Planet Neuroscience

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A Breakdown of Imagined Visuomotor Transformations and Its Neural Correlates in Young Elderly Subjects

Abstract
Several studies have shown age-related changes in motor imagery (MI) in older adults and the associated compensatory brain activation patterns; most of these studies have used explicit MI tasks or implicit MI tasks focused on mental rotation of body parts. Here, we address the effect of ageing on MI for the more complex visuomotor transformations entailed by mentally simulated hand-tool interactions triggered by a grip selection task (GST) for tools used in daily life. We studied 22 young and 22 elderly subjects performing the GST, in which they were asked to report whether they would grip a portrayed tool with an overhand or an underhand grip. We found a behavioral decline in the elderly group, accompanied by reduced activations of the left posterior parietal lobule, in a subregion associated specifically with reaching behavior by previous investigations. No differences were observed in the temporal cortices associated with object semantics. These results suggested a specific age-related vulnerability of the neural substrates, particularly for the imaginary reaching component of the task, rather than for the semantically driven grasping component. The combination of behavioral deficits and reduced activation of specific brain regions speaks in favor of a specific age-associated deficit for the complex imaginary movements required by the GST.
in Cerebral Cortex Advance Access on December 15, 2018 12:00 AM.
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Brain Functional Organization Associated With Language Lateralization

Abstract
Although it is well-established that human language functions are mostly lateralized to the left hemisphere of the brain, little is known about the functional mechanisms underlying such hemispheric dominance. The present study investigated intrinsic organization of the whole brain at rest, by means of functional connectivity and graph theoretical analysis, with the aim to characterize brain functional organization underlying typical and atypical language dominance. We included healthy left-handers, both those with typical left-lateralized language and those with atypical right-lateralized language. Results show that 1) differences between typical and atypical language lateralization are associated with functional connectivity within the language system, particularly with weakened connectivity between left inferior frontal gyrus and several other language-related areas; and 2) for participants with atypical language dominance, the degree of lateralization is linked with multiple functional connectivities and graph theoretical metrics of whole brain organization, including local efficiency and small-worldness. This is the first study, to our knowledge, that linked the degree of language lateralization to global topology of brain networks. These results reveal that typical and atypical language dominance mainly differ in functional connectivity within the language system, and that atypical language dominance is associated with whole-brain organization.
in Cerebral Cortex Advance Access on December 15, 2018 12:00 AM.
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Cytoarchitectonic segregation of human posterior intraparietal and adjacent parieto-occipital sulcus and its relation to visuomotor and cognitive functions

Abstract
Human posterior intraparietal sulcus (pIPS) and adjacent posterior wall of parieto-occipital sulcus (POS) are functionally diverse, serving higher motor, visual and cognitive functions. Its microstructural basis, though, is still largely unknown. A similar or even more pronounced architectonical complexity, as described in monkeys, could be assumed. We cytoarchitectonically mapped the pIPS/POS in 10 human postmortem brains using an observer-independent, quantitative parcellation. 3D-probability maps were generated within MNI reference space and used for functional decoding and meta-analytic coactivation modeling based on the BrainMap database to decode the general structural–functional organization of the areas. Seven cytoarchitectonically distinct areas were identified: five within human pIPS, three on its lateral (hIP4-6) and two on its medial wall (hIP7-8); and two (hPO1, hOc6) in POS. Mediocaudal areas (hIP7, hPO1) were predominantly involved in visual processing, whereas laterorostral areas (hIP4-6, 8) were associated with higher cognitive functions, e.g. counting. This shift was mirrored by systematic changes in connectivity, from temporo-occipital to premotor and prefrontal cortex, and in cytoarchitecture, from prominent Layer IIIc pyramidal cells to homogeneous neuronal distribution. This architectonical mosaic within human pIPS/POS represents a structural basis of its functional and connectional heterogeneity. The new 3D-maps of the areas enable dedicated assessments of structure–function relationships.
in Cerebral Cortex Open Access on December 15, 2018 12:00 AM.
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Organizing principles of whole-brain functional connectivity in zebrafish larvae
Network science has begun to reveal the fundamental principles by which large-scale brain networks are organized, including geometric constraints, a balance between segregative and integrative features, and flexible brain areas. However, it remains unknown whether whole-brain networks imaged at the cellular level are organized according to similar principles. Here, we analyze whole-brain functional networks reconstructed from calcium imaging data recorded in larval zebrafish. Our analyses reveal that functional connections are distance-dependent and that networks exhibit hierarchical modular structure and hubs that span module boundaries. We go on to show that spontaneous network structure places constraints on stimulus-evoked reconfigurations of connections and that networks are highly consistent across individuals. Our analyses reveal, for the first time, basic organizing principles of whole-brain functional brain networks at the microscale. Our overarching methodological framework provides a blueprint for studying the correlated activity at the cellular level using a low-dimensional network representation. Our work forms a conceptual bridge between macro- and microscale network neuroscience and opens myriad paths for future studies to investigate network structure of nervous systems at the cellular level.
in bioRxiv Subject Collection: Neuroscience on December 15, 2018 12:00 AM.
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Multiscale computational model of Achilles tendon wound healing: Untangling the effects of repair and loading

by Kellen Chen, Xiao Hu, Silvia S. Blemker, Jeffrey W. Holmes
Mechanical stimulation of the healing tendon is thought to regulate scar anisotropy and strength and is relatively easy to modulate through physical therapy. However, in vivo studies of various loading protocols in animal models have produced mixed results. To integrate and better understand the available data, we developed a multiscale model of rat Achilles tendon healing that incorporates the effect of changes in the mechanical environment on fibroblast behavior, collagen deposition, and scar formation. We modified an OpenSim model of the rat right hindlimb to estimate physiologic strains in the lateral/medial gastrocnemius and soleus musculo-tendon units during loading and unloading conditions. We used the tendon strains as inputs to a thermodynamic model of stress fiber dynamics that predicts fibroblast alignment, and to determine local collagen synthesis rates according to a response curve derived from in vitro studies. We then used an agent-based model (ABM) of scar formation to integrate these cell-level responses and predict tissue-level collagen alignment and content. We compared our model predictions to experimental data from ten different studies. We found that a single set of cellular response curves can explain features of observed tendon healing across a wide array of reported experiments in rats–including the paradoxical finding that repairing transected tendon reverses the effect of loading on alignment–without fitting model parameters to any data from those experiments. The key to these successful predictions was simulating the specific loading and surgical protocols to predict tissue-level strains, which then guided cellular behaviors according to response curves based on in vitro experiments. Our model results provide a potential explanation for the highly variable responses to mechanical loading reported in the tendon healing literature and may be useful in guiding the design of future experiments and interventions.
in PLOS Computational Biology: New Articles on December 14, 2018 10:00 PM.
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Prediction of antibiotic resistance in <i>Escherichia coli</i> from large-scale pan-genome data

by Danesh Moradigaravand, Martin Palm, Anne Farewell, Ville Mustonen, Jonas Warringer, Leopold Parts
The emergence of microbial antibiotic resistance is a global health threat. In clinical settings, the key to controlling spread of resistant strains is accurate and rapid detection. As traditional culture-based methods are time consuming, genetic approaches have recently been developed for this task. The detection of antibiotic resistance is typically made by measuring a few known determinants previously identified from genome sequencing, and thus requires the prior knowledge of its biological mechanisms. To overcome this limitation, we employed machine learning models to predict resistance to 11 compounds across four classes of antibiotics from existing and novel whole genome sequences of 1936 E. coli strains. We considered a range of methods, and examined population structure, isolation year, gene content, and polymorphism information as predictors. Gradient boosted decision trees consistently outperformed alternative models with an average accuracy of 0.91 on held-out data (range 0.81–0.97). While the best models most frequently employed gene content, an average accuracy score of 0.90 could be obtained using population structure information alone. Single nucleotide variation data were less useful, and significantly improved prediction only for two antibiotics, including ciprofloxacin. These results demonstrate that antibiotic resistance in E. coli can be accurately predicted from whole genome sequences without a priori knowledge of mechanisms, and that both genomic and epidemiological data can be informative. This paves way to integrating machine learning approaches into diagnostic tools in the clinic.
in PLOS Computational Biology: New Articles on December 14, 2018 10:00 PM.
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Corrigendum: Metabotropic Glutamate Receptor 7: A New Therapeutic Target in Neurodevelopmental Disorders
Nicole M. Fisher, Mabel Seto, Craig W. Lindsley, Colleen M. Niswender
in Frontiers in Molecular Neuroscience | New and Recent Articles on December 14, 2018 06:00 PM.
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TAT-Ngn2 Enhances Cognitive Function Recovery and Regulates Caspase-Dependent and Mitochondrial Apoptotic Pathways After Experimental Stroke
Yu Zhao, Jinling Wang, Jiwei Du, Baixiang Li, Xingchun Gou, Jiannan Liu, Lichao Hou, Hanfei Sang, Bin Deng
in Frontiers in Cellular Neuroscience | New and Recent Articles on December 14, 2018 06:00 PM.
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Neuronal correlations in MT and MST impair population decoding of opposite directions of random dot motion
Abstract
The study of neuronal responses to random-dot motion patterns has provided some of the most valuable insights into how the activity of neurons is related to perception. In the opposite directions of motion paradigm, the motion signal strength is decreased by manipulating the coherence of random dot patterns to examine how well the activity of single neurons represents the direction of motion. To extend this paradigm to populations of neurons, studies have used modelling based on data from pairs of neurons, but several important questions require further investigation with larger neuronal datasets. We recorded neuronal populations in the middle temporal (MT) and medial superior temporal (MST) areas of anaesthetized marmosets with electrode arrays, while varying the coherence of random dot patterns in two opposite directions of motion (left and right). Using the spike rates of simultaneously recorded neurons, we decoded the direction of motion at each level of coherence with linear classifiers. We found that the presence of correlations had a detrimental effect to decoding performance, but that learning the correlation structure produced better decoding performance compared to decoders that ignored the correlation structure. We also found that reducing motion coherence increased neuronal correlations, but decoders did not need to be optimized for each coherence level. Finally, we showed that decoder weights depend of left-right selectivity at 100% coherence, rather than the preferred direction. These results have implications for understanding how the information encoded by populations of neurons is affected by correlations in spiking activity.
Significance Statement Many studies have examined how the spiking activity of single neurons can encode stimulus features, such the direction of motion of visual stimuli. However, majority of such studies to date have only recorded from a small number of neurons at the same time, meaning that one cannot adequately account for the trial-to-trial correlations in spiking activity between neurons. Using multi-channel recordings, we were able to measure the neuronal correlations, and their effects on population coding of stimulus features. Our results have implications on the way which neural populations must be read-out in order to maximize information.

in RSS PAP on December 14, 2018 05:55 PM.
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Genotype, extrapyramidal features and severity of variant Ataxia‐Telangiectasia

Abstract

Objective

Variant Ataxia‐Telangiectasia is caused by mutations that allow some retained ATM kinase activity. Here, we describe the clinical features of the largest established cohort of individuals with variant Ataxia‐Telangiectasia and explore genotype‐phenotype correlations.

Methods

Cross‐sectional data were collected retrospectively. Patients were classified as variant Ataxia‐Telangiectasia based on retained ATM kinase activity.

Results

The study includes 57 individuals. Mean age at assessment was 37.5 years. Most had their first symptoms by age ten (81%). There was a diagnostic delay of more than ten years in 68% and more than 20 years in a third of probands.

Disease severity was mild in a third of patients and 43% were still ambulant 20 years after disease onset. Only a third had predominant ataxia and 18% had a pure extrapyramidal presentation. Individuals with extrapyramidal presentations had milder neurological disease severity. There were no significant respiratory or immunological complications, but 25% of individuals had a history of malignancy. Missense mutations were associated with milder neurological disease severity but with a higher risk of malignancy, compared to leaky splice site mutations.

Interpretation

Individuals with variant Ataxia‐Telangiectasia require malignancy surveillance and tailored management. However, our data suggest the condition may sometimes be mis‐ or underdiagnosed due to atypical features, including exclusive extrapyramidal symptoms, normal eye movements and normal AFP levels in some individuals. Missense mutations are associated with milder neurological presentations but a particularly high malignancy risk and it is important for clinicians to be aware of these phenotypes.

This article is protected by copyright. All rights reserved.

in Wiley: Annals of Neurology: Table of Contents on December 14, 2018 11:02 AM.
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DNA damage signatures in peripheral blood cells (PBMC) as biomarkers in prodromal Huntington's disease

Abstract

Easily accessible biomarkers in Huntington disease (HD) are actively searched. We investigated telomere length (TL) and DNA double−strand breaks (histone variant pγ−H2AX) as predictive disease biomarkers in peripheral blood mononuclear cells (PBMC) from 25 pre‐manifest, 58 HD patients, with similar CAG expansion in the huntingtin gene (HTT) gene and 44 healthy controls (HC).

PBMC from PRE‐HD and HD groups showed shorter telomeres (p<0.0001) and a significant increase of pγ−H2AX compared to the controls (p<0.0001). The levels of pγ‐H2AX correlated robustly with the presence of the mutated gene in PRE‐HD and HD. The availability of a potentially reversible biomarker (pγ−H2AX) in the pre−manifest stage of HD, negligible in HC, provides a novel tool to monitor pre−manifest subjects and find patient−specific drugs.

This article is protected by copyright. All rights reserved.

in Wiley: Annals of Neurology: Table of Contents on December 14, 2018 11:01 AM.
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The impact of Aβ and tau on prospective cognitive decline in older individuals

Abstract

Objectives

Amyloid‐beta (Aβ) and tau pathologies are commonly observed among clinically normal older individuals at post‐mortem and can now be detected with in vivo neuroimaging. The association and interaction of these proteinopathies with prospective cognitive decline in normal aging and preclinical Alzheimer's disease (AD) remains to be fully elucidated.

Methods

One hundred and thirty‐seven older individuals (age=76.3±6.22 years) participating in the Harvard Aging Brain Study underwent Aβ (¹¹C‐Pittsburgh Compound B) and tau (¹⁸F‐Flortaucipir) positron emission tomography (PET) with prospective neuropsychological assessments following PET imaging (mean number of cognitive visits = 2.8±1.1). Tau and Aβ PET measures were assessed in regions of interest (ROI) as well as vertex‐wise map analyses. Cognitive change was evaluated with Memory and Executive Function composites.

Results

Higher levels of Aβ and tau were both associated with greater memory decline, but not with change in executive function. Higher cortical Aβ was associated with higher tau levels in all ROI, independent of age, and very elevated levels of tau were observed primarily in CN with elevated Aβ. A significant interaction between tau and Aβ was observed in both ROI and map level analyses, such that rapid prospective memory decline was observed in participants who had high levels of both pathologies.

Interpretation

Our results are consistent with the supposition that both Aβ and tau are necessary for memory decline in the preclinical stages of AD. These findings may be relevant for disambiguating aging and early cognitive manifestations of AD, and to inform secondary prevention trials in preclinical AD.

This article is protected by copyright. All rights reserved.

in Wiley: Annals of Neurology: Table of Contents on December 14, 2018 11:00 AM.
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Cognitive and Pathological Influences of Tau Pathology in Lewy Body Disorders

ABSTRACT

Objective

To use digital histology in a large autopsy cohort of Lewy Body Disorder (LBD) patients with dementia to test the hypotheses that co‐occurring Alzheimer's disease (AD) pathology impacts the anatomic distribution of α‐synuclein (SYN) pathology and that co‐occurring neocortical tau pathology in LBD associates with worse cognitive performance and occurs in a pattern differing from AD.

Methods

Fifty‐five autopsy‐confirmed LBD (PDD: 36, DLB:19) patients and 25 AD patients were studied. LBD patients were categorized as having moderate/severe AD co‐pathology (SYN+AD=20) or little/no AD co‐pathology (SYN‐AD=35). Digital measures of tau, Aβ, and SYN histopathology in neocortical and subcortical/limbic regions were compared between groups and related to antemortem cognitive testing.

Results

SYN burden was higher in SYN+AD than SYN‐AD in each neocortical region (F(1,54)=5.6‐6.0,p<0.02) but was equivalent in entorhinal cortex and putamen (F(1,43‐49)=0.7‐1.7,p>0.2). SYN+AD performed worse than SYN‐AD on a temporal‐lobe mediated naming task (t(27)=2.1,p=0.04). Antemortem cognitive test scores inversely correlated with tau burden (r=‐0.39 to ‐0.68,p<0.05). AD had higher tau than SYN+AD in all regions (F(1,43)=12.8‐97.2,p<.001); however, SYN+AD had a greater proportion of tau in the temporal neocortex than AD, (t(41)=2.0,p<.05) whereas AD had a greater proportion of tau in the frontal neocortex than SYN+AD (t(41)=3.3,p<0.002). SYN+AD had similar severity and distribution of neocortical Aβ compared to AD (F(1,40‐43)=1.6‐2.0,p>.1).

Interpretation

LBD patients with AD co‐pathology harbor greater neocortical SYN pathology. Regional tau pathology relates to cognitive performance in LBD dementia, and its distribution may diverge from pure AD. Tau co‐pathology contributes uniquely to the heterogeneity of cognitive impairment in LBD.

This article is protected by copyright. All rights reserved.

in Wiley: Annals of Neurology: Table of Contents on December 14, 2018 10:59 AM.
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Functional Status of Neuronal Calcium Sensor-1 Is Modulated by Zinc Binding
Philipp O. Tsvetkov, Andrei Yu. Roman, Viktoriia E. Baksheeva, Aliya A. Nazipova, Marina P. Shevelyova, Vasiliy I. Vladimirov, Michelle F. Buyanova, Dmitry V. Zinchenko, Andrey A. Zamyatnin, François Devred, Andrey V. Golovin, Sergei E. Permyakov, Evgeni Yu. Zernii
in Frontiers in Molecular Neuroscience | New and Recent Articles on December 14, 2018 06:00 AM.
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Molecular Mechanisms of Synaptotoxicity and Neuroinflammation in Alzheimer’s Disease
Mikael Marttinen, Mari Takalo, Teemu Natunen, Rebekka Wittrahm, Sami Gabbouj, Susanna Kemppainen, Ville Leinonen, Heikki Tanila, Annakaisa Haapasalo, Mikko Hiltunen
in Frontiers in Neuroscience | Neurodegeneration section | New and Recent Articles on December 14, 2018 06:00 AM.
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A Metric for Evaluating Neural Input Representation in Supervised Learning Networks
Richard R. Carrillo, Francisco Naveros, Eduardo Ros, Niceto R. Luque
in Frontiers in Neuroscience | Systems Biology section | New and Recent Articles on December 14, 2018 06:00 AM.
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Advances in Parkinson’s Disease: 200 Years Later
Natalia López-González Del Rey, Ana Quiroga-Varela, Elisa Garbayo, Iria Carballo-Carbajal, Rubén Fernández-Santiago, Mariana H. G. Monje, Inés Trigo-Damas, María J. Blanco-Prieto, Javier Blesa
in Frontiers in Neuroanatomy | New and Recent Articles on December 14, 2018 06:00 AM.
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Informing Artificial Intelligence Generative Techniques using Cognitive Theories of Human Creativity. (arXiv:1812.05556v1 [cs.AI])

The common view that our creativity is what makes us uniquely human suggests that incorporating research on human creativity into generative deep learning techniques might be a fruitful avenue for making their outputs more compelling and human-like. Using an original synthesis of Deep Dream-based convolutional neural networks and cognitive based computational art rendering systems, we show how honing theory, intrinsic motivation, and the notion of a 'seed incident' can be implemented computationally, and demonstrate their impact on the resulting generative art. Conversely, we discuss how explorations in deep learn-ing convolutional neural net generative systems can inform our understanding of human creativity. We conclude with ideas for further cross-fertilization between AI based computational creativity and psychology of creativity.

in q-bio.NC updates on arXiv.org on December 14, 2018 01:30 AM.
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Chaotic Dynamics Enhance the Sensitivity of Inner Ear Hair Cells. (arXiv:1812.05156v1 [q-bio.NC])

Hair cells of the auditory and vestibular systems are capable of detecting sounds that induce sub-nanometer vibrations of the hair bundle, below the stochastic noise levels of the surrounding fluid. Hair cells of certain species are also known to oscillate without external stimulation, indicating the presence of an underlying active mechanism. We previously demonstrated that these spontaneous oscillations exhibit chaotic dynamics. By varying the Calcium concentration and the viscosity of the Endolymph solution, we are able to modulate the degree of chaos in the hair cell dynamics. We find that the hair cell is most sensitive to a stimulus of small amplitude when it is poised in the weakly chaotic regime. Further, we show that the response time to a force step decreases with increasing levels of chaos. These results agree well with our numerical simulations of a chaotic Hopf oscillator and suggest that chaos may be responsible for the extreme sensitivity and temporal resolution of hair cells.

in q-bio.NC updates on arXiv.org on December 14, 2018 01:30 AM.
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Disarming the guards of change

Disarming the guards of change
Disarming the guards of change, Published online: 14 December 2018; doi:10.1038/s41583-018-0114-0
Repetitive sensory input induces long-term potentiation of pyramidal cell synapses in mouse somatosensory cortex by activation of higher-order thalamic projections and disinhibition of local interneurons.
in Nature Reviews Neuroscience - Issue - nature.com science feeds on December 14, 2018 12:00 AM.
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Portraits of communication in neuronal networks

Portraits of communication in neuronal networks
Portraits of communication in neuronal networks, Published online: 14 December 2018; doi:10.1038/s41583-018-0094-0
In this Opinion article, Hahn, Kumar and colleagues propose that synchrony- and oscillation-based communication between brain networks can be described by a common theoretical framework. They also suggest a mechanism for control of the flow of information in the brain through nesting of slow and fast oscillations.
in Nature Reviews Neuroscience - Issue - nature.com science feeds on December 14, 2018 12:00 AM.
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Folding mutations suppress early beta-cell proliferation
Exploring how proliferation and maturation of beta-cells can be impaired after birth will shed light on the origins of various forms of diabetes.
in eLife: latest articles on December 14, 2018 12:00 AM.
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Genetic analysis reveals functions of atypical polyubiquitin chains
Although polyubiquitin chains linked through all lysines of ubiquitin exist, specific functions are well-established only for lysine-48 and lysine-63 linkages in Saccharomyces cerevisiae. To uncover pathways regulated by distinct linkages, genetic interactions between a gene deletion library and a panel of lysine-to-arginine ubiquitin mutants were systematically identified. The K11R mutant had strong genetic interactions with threonine biosynthetic genes. Consistently, we found that K11R mutants import threonine poorly. The K11R mutant also exhibited a strong genetic interaction with a subunit of the anaphase-promoting complex (APC), suggesting a role in cell cycle regulation. K11-linkages are important for vertebrate APC function, but this was not previously described in yeast. We show that the yeast APC also modifies substrates with K11-linkages in vitro, and that those chains contribute to normal APC-substrate turnover in vivo. This study reveals comprehensive genetic interactomes of polyubiquitin chains and characterizes the role of K11-chains in two biological pathways.
in eLife: latest articles on December 14, 2018 12:00 AM.
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Tuning of delta-protocadherin adhesion through combinatorial diversity
The delta-protocadherins (δ-Pcdhs) play key roles in neural development, and expression studies suggest they are expressed in combination within neurons. The extent of this combinatorial diversity, and how these combinations influence cell adhesion, is poorly understood. We show that individual mouse olfactory sensory neurons express 0-7 δ-Pcdhs. Despite this apparent combinatorial complexity, K562 cell aggregation assays revealed simple principles mediate tuning of δ-Pcdh adhesion. Cells can vary the number of δ-Pcdhs expressed, the level of surface expression, and which δ-Pcdhs are expressed, as different members possess distinct apparent adhesive affinities. These principles contrast with those identified previously for the clustered protocadherins (cPcdhs), where the particular combination of cPcdhs expressed does not appear to be a critical factor. Despite these differences, we show δ-Pcdhs can modify cPcdh adhesion. Our studies show how intra- and interfamily interactions can greatly amplify the impact of this small subfamily on neuronal function.
in eLife: latest articles on December 14, 2018 12:00 AM.
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BUB-1 promotes amphitelic chromosome biorientation via multiple activities at the kinetochore
Accurate chromosome segregation relies on bioriented amphitelic attachments of chromosomes to microtubules of the mitotic spindle, in which sister chromatids are connected to opposite spindle poles. BUB-1 is a protein of the Spindle Assembly Checkpoint (SAC) that coordinates chromosome attachment with anaphase onset. BUB-1 is also required for accurate sister chromatid segregation independently of its SAC function, but the underlying mechanism remains unclear. Here we show that, in Caenorhabditis elegans embryos, BUB-1 accelerates the establishment of non-merotelic end-on kinetochore-microtubule attachments by recruiting the RZZ complex and its downstream partner dynein-dynactin at the kinetochore. In parallel, BUB-1 limits attachment maturation by the SKA complex. This activity opposes kinetochore-microtubule attachment stabilisation promoted by CLS-2^CLASP-dependent kinetochore-microtubule assembly. BUB-1 is therefore a SAC component that coordinates the function of multiple downstream kinetochore-associated proteins to ensure accurate chromosome segregation.
in eLife: latest articles on December 14, 2018 12:00 AM.
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Neural circuitry of a polycystin-mediated hydrodynamic startle response for predator avoidance
Startle responses triggered by aversive stimuli including predators are widespread across animals. These coordinated whole-body actions require the rapid and simultaneous activation of a large number of muscles. Here we study a startle response in a planktonic larva to understand the whole-body circuit implementation of the behaviour. Upon encountering water vibrations, larvae of the annelid Platynereis close their locomotor cilia and simultaneously raise the parapodia. The response is mediated by collar receptor neurons expressing the polycystins PKD1-1 and PKD2-1. CRISPR-generated PKD1-1 and PKD2-1 mutant larvae do not startle and fall prey to a copepod predator at a higher rate. Reconstruction of the whole-body connectome of the collar-receptor-cell circuitry revealed converging feedforward circuits to the ciliary bands and muscles. The wiring diagram suggests circuit mechanisms for the intersegmental and left-right coordination of the response. Our results reveal how polycystin-mediated mechanosensation can trigger a coordinated whole-body effector response involved in predator avoidance.
in eLife: latest articles on December 14, 2018 12:00 AM.
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Prediction error and repetition suppression have distinct effects on neural representations of visual information
Predictive coding theories argue that recent experience establishes expectations in the brain that generate prediction errors when violated. Prediction errors provide a possible explanation for repetition suppression, where evoked neural activity is attenuated across repeated presentations of the same stimulus. The predictive coding account argues repetition suppression arises because repeated stimuli are expected, whereas non-repeated stimuli are unexpected and thus elicit larger neural responses. Here we employed electroencephalography in humans to test the predictive coding account of repetition suppression by presenting sequences of visual gratings with orientations that were expected either to repeat or change in separate blocks of trials. We applied multivariate forward modelling to determine how orientation selectivity was affected by repetition and prediction. Unexpected stimuli were associated with significantly enhanced orientation selectivity, whereas selectivity was unaffected for repeated stimuli. Our results suggest that repetition suppression and expectation have separable effects on neural representations of visual feature information.
in eLife: latest articles on December 14, 2018 12:00 AM.
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Offline replay supports planning in human reinforcement learning
Making decisions in sequentially structured tasks requires integrating distally acquired information. The extensive computational cost of such integration challenges planning methods that integrate online, at decision time. Furthermore, it remains unclear whether 'offline' integration during replay supports planning, and if so which memories should be replayed. Inspired by machine learning, we propose that (a) offline replay of trajectories facilitates integrating representations that guide decisions, and (b) unsigned prediction errors (uncertainty) trigger such integrative replay. We designed a 2-step revaluation task for fMRI, whereby participants needed to integrate changes in rewards with past knowledge to optimally replan decisions. As predicted, we found that (a) multi-voxel pattern evidence for off-task replay predicts subsequent replanning; (b) neural sensitivity to uncertainty predicts subsequent replay and replanning; (c) off-task hippocampus and anterior cingulate activity increase when revaluation is required. These findings elucidate how the brain leverages offline mechanisms in planning and goal-directed behavior under uncertainty.
in eLife: latest articles on December 14, 2018 12:00 AM.
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The cortico-striatal circuit regulates sensorimotor gating via Disc1/Huntingtin-mediated Bdnf transport
Sensorimotor information processing that underlies normal cognitive and behavioral traits is dysregulated across a subset of neurological and psychiatric disorders. The cross-disease deficit in sensorimotor gating poses a unique opportunity to integrate hierarchical findings at molecular, cellular, through circuitry levels to obtain an in-depth mechanistic understanding of this process that contributes to brain physiology and pathophysiology beyond categorical segmentation of brain disorders. Based on circuitry recording with wild-type mice, we demonstrated that the cortico-striatal projection mediates sensorimotor gating responses during prepulse inhibition (PPI) task. We also found that these circuitry responses were disrupted in Disc1 locus-impairment (LI) mice, a model representing neuropsychiatric conditions. Thus, we hypothesized that Disc1-mediated molecular and cellular machinery along the cortico-striatal circuit may regulate sensorimotor gating. Anatomical and biochemical analyses of Disc1-LI mice revealed attenuated Bdnf transport along the cortico-striatal circuit. Pharmacologically augmenting Bdnf transport by chronic lithium administration, in part via Ser-421 phosphorylation of Huntingtin (Htt) and its integration into the motor machinery, restored the striatal Bdnf levels and PPI deficits in Disc1-LI mice, suggesting that the Bdnf transport attenuation mechanistically underlies the circuitry and behavioral deficits. These results also shed light on a novel mechanism and utility of lithium that is currently used as a major mood stabilizer in clinical settings. Collectively, the present study illustrates integrative biological mechanisms for sensorimotor gating, underscoring the cross-disease nature of this behavioral dimension and translational utility of the findings under the era of precision medicine in brain disorders.
in bioRxiv Subject Collection: Neuroscience on December 14, 2018 12:00 AM.
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Analysing linear multivariate pattern transformations in neuroimaging data
Most connectivity metrics in neuroimaging research reduce multivariate activity patterns in regions-of-interests (ROIs) to one dimension, which leads to a loss of information. Importantly, it prevents us from investigating the transformations between patterns in different ROIs. Here, we applied linear estimation theory in order to robustly estimate the linear transformations between multivariate fMRI patterns with a cross-validated Tikhonov regularisation approach. We derived three novel metrics that describe different features of these voxel-by-voxel mappings: goodness-of-fit, sparsity and pattern deformation. The goodness-of-fit describes the degree to which the patterns in an input region can be described as a linear transformation of patterns in an output region. The sparsity metric, which relies on a Monte Carlo procedure, was introduced in order to test whether the transformation mostly consists of one-to-one mappings between voxels in different regions. Furthermore, we defined a metric for pattern deformation, i.e. the degree to which the transformation rotates or rescales the input patterns. As a proof of concept, we applied these metrics to an event-related fMRI data set consisting of four subjects that has been used in previous studies. We focused on the transformations from early visual cortex (EVC) to inferior temporal cortex (ITC), fusiform face area (FFA) and parahippocampal place area (PPA). Our results suggest that the estimated linear mappings are able to explain a significant amount of variance of the three output ROIs. The transformation from EVC to ITC shows the highest goodness-of-fit, and those from EVC to FFA and PPA show the expected preference for faces and places as well as animate and inanimate objects, respectively. The pattern transformations are sparse, but sparsity is lower than would have been expected for one-to-one mappings, thus suggesting the presence of one-to-few voxel mappings. ITC, FFA and PPA patterns are not simple rotations of an EVC pattern, indicating that the corresponding transformations amplify or dampen certain dimensions of the input patterns. While our results are only based on a small number of subjects, they show that our pattern transformation metrics can describe novel aspects of multivariate functional connectivity in neuroimaging data.
in bioRxiv Subject Collection: Neuroscience on December 14, 2018 12:00 AM.
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Reading eye movements in traumatic brain injury
Background: The aim of our study was to measure the reading eye movements in subjects with traumatic brain injury using ReadAlyzer. ReadAlyzer is an objective eye movement recording device that tracks the eye movements while reading. Methods: Reading eye movements were measured using ReadAlyzer in 30 subjects with traumatic brain injury (mild, moderate and severe) who had binocular vision and reading related symptoms and 60 asymptomatic controls. Results: There was a significant decrease in reading eye movement parameters in subjects with traumatic brain injury compared to controls. Reading eye movement parameters were represented in median (IQR). Subjects with traumatic brain injury presented with an increased number of fixations/100 words: 137 (106-159) and regressions/100 words: 24 (12-36), and reduced reading rate 154 (128-173) words per minute. They also had a lesser grade level equivalent: 4.0 (3.0-7.0) and reduced comprehension: 70 (60-80) percentage (Mann-Whitney U test, p<0.05). Reading eye movement parameters were significantly affected in mild and moderate-severe traumatic brain injury subjects compared to controls (Kruskal-Wallis test, p<0.05). Conclusion: Reading eye movement performance using ReadAlyzer was found to be decreased in traumatic brain injury. Reading assessment may serve as a clinical measure to understand the oculomotor system due to traumatic brain injury.
in bioRxiv Subject Collection: Neuroscience on December 14, 2018 12:00 AM.
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Maladaptive coping strategies and neuroticism mediate the relationship between 5HTT-LPR polymorphisms and symptoms of anxiety in elite athletes.
Previous studies have suggested that genetic factors, personality traits and coping strategies might play independent and interacting roles in influencing stress-related anxiety symptoms. The aim of this study was to examine whether Neuroticism and maladaptive coping strategies mediate the association between the serotonin transporter gene-linked polymorphic region (5HTT-LPR) and symptoms of anxiety and depression in elite athletes who experience high levels of competitive stress. One hundred and thirty-three participants were genotyped for the 5-HTTLPR polymorphism and then asked to complete the Cope Orientation to Problems Experienced Inventory and the NEO Five-Factor Inventory. A path analysis was used to test the aforementioned hypothesis. The 5HTT-LPR was significantly associated with Neuroticism, the coping strategy of Focus on and Venting of Emotions (FVE) and symptoms of anxiety. FVE and Neuroticism mediated the association between the 5HTT-LPR and symptoms of anxiety (i.e., Cognitive Anxiety and Emotional Arousal Control). Also, Neuroticism was a mediator of the association between the 5HTT-LPR and FVE. Finally, FVE also mediated effects on the relationship between Neuroticism and symptoms of anxiety. Results suggest that the 5HTT-LPR may affect the susceptibility to develop symptoms of anxiety in elite athletes indirectly through mediation by FVE and Neuroticism.
in bioRxiv Subject Collection: Neuroscience on December 14, 2018 12:00 AM.
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Optogenetic stimulation of long-range inputs and functional characterization of connectivity in patch-clamp recordings in mouse brain slices
Knowledge of cell type specific synaptic connectivity is a crucial prerequisite for understanding brain wide neuronal circuits. The functional investigation of long-range connections requires targeted recordings of single neurons combined with the specific stimulation of identified distant inputs. This is often difficult to achieve with conventional, electrical stimulation techniques, because axons from converging upstream brain areas may intermingle in the target region. The stereotaxic targeting of a specific brain region for virus-mediated expression of light sensitive ion channels allows to selectively stimulate axons coming from that region with light. Intracerebral stereotaxic injections can be used in well-delimited structures, such as the anterodorsal thalamic nuclei, and also in other subcortical or cortical areas throughout the brain. Here we describe a set of techniques for precise stereotaxic injection of viral vectors expressing channelrhodopsin in the anterodorsal thalamus, followed by photostimulation of their axon terminals in hippocampal slices. In combination with whole-cell patch clamp recording from a postsynaptically connected presubicular neuron, photostimulation of thalamic axons allows the detection of functional synaptic connections, their pharmacological characterization, and the evaluation of their strength in the brain slice preparation. We demonstrate that axons originating in the anterodorsal thalamus ramify densely in presubicular layers 1 and 3. The photostimulation of Chronos expressing thalamic axon terminals in presubiculum initiates short latency postsynaptic responses in a presubicular layer3 neuron, indicating a monosynaptic connection. In addition, biocytin filling of the recorded neuron and posthoc revelation confirms the layer localization and pyramidal morphology of the postsynaptic neuron. Taken together, the optogenetic stimulation of long-range inputs in ex vivo brain slices is a useful method to determine the cell-type specific functional connectivity from distant brain regions.
in bioRxiv Subject Collection: Neuroscience on December 14, 2018 12:00 AM.
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G-quadruplex forming sequences in the genome of all known human viruses: A comprehensive guide

by Enrico Lavezzo, Michele Berselli, Ilaria Frasson, Rosalba Perrone, Giorgio Palù, Alessandra R. Brazzale, Sara N. Richter, Stefano Toppo
G-quadruplexes are non-canonical nucleic-acid structures that control transcription, replication, and recombination in organisms. G-quadruplexes are present in eukaryotes, prokaryotes, and viruses. In the latter, mounting evidence indicates their key biological activity. Since data on viruses are scattered, we here present a comprehensive analysis of potential quadruplex-forming sequences (PQS) in the genome of all known viruses that can infect humans. We show that occurrence and location of PQSs are features characteristic of each virus class and family. Our statistical analysis proves that their presence within the viral genome is orderly arranged, as indicated by the possibility to correctly assign up to two-thirds of viruses to their exact class based on the PQS classification. For each virus we provide: i) the list of all PQS present in the genome (positive and negative strands), ii) their position in the viral genome, iii) the degree of conservation among strains of each PQS in its genome context, iv) the statistical significance of PQS abundance. This information is accessible from a database to allow the easy navigation of the results: http://www.medcomp.medicina.unipd.it/main_site/doku.php?id=g4virus. The availability of these data will greatly expedite research on G-quadruplex in viruses, with the possibility to accelerate finding therapeutic opportunities to numerous and some fearsome human diseases.
in PLOS Computational Biology: New Articles on December 13, 2018 10:00 PM.
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Eleven quick tips to build a usable REST API for life sciences

by Aleksandra Tarkowska, Denise Carvalho-Silva, Charles E. Cook, Edd Turner, Robert D. Finn, Andrew D. Yates

in PLOS Computational Biology: New Articles on December 13, 2018 10:00 PM.
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Full-Length Envelope Analyzer (FLEA): A tool for longitudinal analysis of viral amplicons

by Kemal Eren, Steven Weaver, Robert Ketteringham, Morné Valentyn, Melissa Laird Smith, Venkatesh Kumar, Sanjay Mohan, Sergei L. Kosakovsky Pond, Ben Murrell
Next generation sequencing of viral populations has advanced our understanding of viral population dynamics, the development of drug resistance, and escape from host immune responses. Many applications require complete gene sequences, which can be impossible to reconstruct from short reads. HIV env, the protein of interest for HIV vaccine studies, is exceptionally challenging for long-read sequencing and analysis due to its length, high substitution rate, and extensive indel variation. While long-read sequencing is attractive in this setting, the analysis of such data is not well handled by existing methods. To address this, we introduce FLEA (Full-Length Envelope Analyzer), which performs end-to-end analysis and visualization of long-read sequencing data. FLEA consists of both a pipeline (optionally run on a high-performance cluster), and a client-side web application that provides interactive results. The pipeline transforms FASTQ reads into high-quality consensus sequences (HQCSs) and uses them to build a codon-aware multiple sequence alignment. The resulting alignment is then used to infer phylogenies, selection pressure, and evolutionary dynamics. The web application provides publication-quality plots and interactive visualizations, including an annotated viral alignment browser, time series plots of evolutionary dynamics, visualizations of gene-wide selective pressures (such as dN/dS) across time and across protein structure, and a phylogenetic tree browser. We demonstrate how FLEA may be used to process Pacific Biosciences HIV env data and describe recent examples of its use. Simulations show how FLEA dramatically reduces the error rate of this sequencing platform, providing an accurate portrait of complex and variable HIV env populations. A public instance of FLEA is hosted at http://flea.datamonkey.org. The Python source code for the FLEA pipeline can be found at https://github.com/veg/flea-pipeline. The client-side application is available at https://github.com/veg/flea-web-app. A live demo of the P018 results can be found at http://flea.murrell.group/view/P018.
in PLOS Computational Biology: New Articles on December 13, 2018 10:00 PM.
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Coherent chaos in a recurrent neural network with structured connectivity

by Itamar Daniel Landau, Haim Sompolinsky
We present a simple model for coherent, spatially correlated chaos in a recurrent neural network. Networks of randomly connected neurons exhibit chaotic fluctuations and have been studied as a model for capturing the temporal variability of cortical activity. The dynamics generated by such networks, however, are spatially uncorrelated and do not generate coherent fluctuations, which are commonly observed across spatial scales of the neocortex. In our model we introduce a structured component of connectivity, in addition to random connections, which effectively embeds a feedforward structure via unidirectional coupling between a pair of orthogonal modes. Local fluctuations driven by the random connectivity are summed by an output mode and drive coherent activity along an input mode. The orthogonality between input and output mode preserves chaotic fluctuations by preventing feedback loops. In the regime of weak structured connectivity we apply a perturbative approach to solve the dynamic mean-field equations, showing that in this regime coherent fluctuations are driven passively by the chaos of local residual fluctuations. When we introduce a row balance constraint on the random connectivity, stronger structured connectivity puts the network in a distinct dynamical regime of self-tuned coherent chaos. In this regime the coherent component of the dynamics self-adjusts intermittently to yield periods of slow, highly coherent chaos. The dynamics display longer time-scales and switching-like activity. We show how in this regime the dynamics depend qualitatively on the particular realization of the connectivity matrix: a complex leading eigenvalue can yield coherent oscillatory chaos while a real leading eigenvalue can yield chaos with broken symmetry. The level of coherence grows with increasing strength of structured connectivity until the dynamics are almost entirely constrained to a single spatial mode. We examine the effects of network-size scaling and show that these results are not finite-size effects. Finally, we show that in the regime of weak structured connectivity, coherent chaos emerges also for a generalized structured connectivity with multiple input-output modes.
in PLOS Computational Biology: New Articles on December 13, 2018 10:00 PM.
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Tac1-Expressing Neurons in the Periaqueductal Gray Facilitate the Itch-Scratching Cycle via Descending Regulation
Gao et al. demonstrate that Tac1-expressing neurons in the l/vlPAG modulate spinal itch processing via a descending pathway. These neurons represent a critical component in the neural circuit that drives the itch-scratching cycle.
in Neuron on December 13, 2018 06:00 PM.
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Transcriptomic Analysis of Zebrafish TDP-43 Transgenic Lines
Alexandra Lissouba, Meijiang Liao, Edor Kabashi, Pierre Drapeau
in Frontiers in Molecular Neuroscience | New and Recent Articles on December 13, 2018 06:00 PM.
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Association of GALC, ZNF184, IL1R2 and ELOVL7 With Parkinson’s Disease in Southern Chinese
Gen Li, Shishuang Cui, Juanjuan Du, Jin Liu, Pingchen Zhang, Yang Fu, Yixi He, Haiyan Zhou, Jianfang Ma, Shengdi Chen
in Frontiers in Aging Neuroscience | New and Recent Articles on December 13, 2018 06:00 PM.
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The Representation of White Matter in the Central Nervous System
Robert Baud, Pierre Sprumont, Hans J. ten Donkelaar
in Frontiers in Neuroanatomy | New and Recent Articles on December 13, 2018 06:00 PM.
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Primary afferent-derived BDNF contributes minimally to the processing of pain and itch
ABSTRACT
Brain-derived neurotrophic factor (BDNF) is a critical contributor to neuronal growth, development, learning and memory. Though extensively studied in the brain, BDNF is also expressed by primary afferent sensory neurons in the peripheral nervous system. Unfortunately, anatomical and functional studies of primary afferent-derived BDNF have been limited by the availability of appropriate molecular tools. Here we used targeted, inducible molecular approaches to characterize the expression pattern of primary afferent BDNF and the extent to which it contributes to a variety of pain and itch behaviors. Using a BDNF-LacZ reporter mouse, we found that BDNF is expressed primarily by myelinated primary afferents and has limited overlap with the major peptidergic and non-peptidergic subclasses of nociceptors and pruritoceptors. We also observed extensive neuronal, but not glial, expression in the spinal cord dorsal horn. In addition, because BDNF null mice are not viable and even Cre-mediated deletion of BDNF from sensory neurons could have developmental consequences, here we deleted BDNF selectively from sensory neurons, in the adult, using an advillin-Cre-ER line crossed to floxed BDNF mice. We found that BDNF deletion in the adult altered few itch or acute and chronic pain behaviors, beyond sexually dimorphic phenotypes in the tail immersion, histamine and formalin tests. Based on the anatomical distribution of sensory neuron-derived BDNF and its limited contribution to pain and itch processing, we suggest that future studies of primary afferent-derived BDNF should examine behaviors evoked by activation of myelinated primary afferents.
SIGNIFICANCE STATEMENT The neurotrophin brain-derived neurotrophic factor (BDNF) is a critical contributor to neuronal growth, development and synaptic plasticity and its expression in primary sensory neurons has been implicated in pain processing. However, there is little consensus as to the sensory neuron subtypes that express BDNF or whether sensory neuron-derived BDNF facilitates or inhibits pain generation. Here we used a BDNF reporter mouse and demonstrate that BDNF predominates in myelinated sensory neurons and is expressed in many spinal cord dorsal horn neurons. In addition, in studies in which BDNF was deleted, in the adult, from all sensory neurons, we found limited deficits in pain or itch processing.

in RSS PAP on December 13, 2018 04:57 PM.
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Neuroplastic Changes in Older Adults Performing Cooperative Hand Movements
Lars Michels, Volker Dietz, Alexandra Schättin, Miriam Schrafl-Altermatt
in Frontiers in Human Neuroscience | New and Recent Articles on December 13, 2018 12:00 PM.
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Alterations in Brain Network Topology and Structural-Functional Connectome Coupling Relate to Cognitive Impairment
Juan Wang, Reza Khosrowabadi, Kwun Kei Ng, Zhaoping Hong, Joanna Su Xian Chong, Yijun Wang, Chun-Yin Chen, Saima Hilal, Narayanaswamy Venketasubramanian, Tien Yin Wong, Christopher Li-Hsian Chen, Mohammad Kamran Ikram, Juan Zhou
in Frontiers in Aging Neuroscience | New and Recent Articles on December 13, 2018 12:00 PM.
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Semantic Features Reveal Different Networks During Word Processing: An EEG Source Localization Study
Mansoureh Fahimi Hnazaee, Elvira Khachatryan, Marc M. Van Hulle
in Frontiers in Human Neuroscience | New and Recent Articles on December 13, 2018 06:00 AM.
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Investigating Neural Sensorimotor Mechanisms Underlying Flight Expertise in Pilots: Preliminary Data From an EEG Study
Mariateresa Sestito, Assaf Harel, Jeff Nador, John Flach
in Frontiers in Human Neuroscience | New and Recent Articles on December 13, 2018 06:00 AM.
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A Similarity-Based Process for Human Judgment in the Parietal Cortex
Linnea Karlsson Wirebring, Sara Stillesjö, Johan Eriksson, Peter Juslin, Lars Nyberg
in Frontiers in Human Neuroscience | New and Recent Articles on December 13, 2018 06:00 AM.
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Activated Microglia Disrupt the Blood-Brain Barrier and Induce Chemokines and Cytokines in a Rat in vitro Model
Yukari Shigemoto-Mogami, Kazue Hoshikawa, Kaoru Sato
in Frontiers in Cellular Neuroscience | New and Recent Articles on December 13, 2018 06:00 AM.
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NGF-Dependent Changes in Ubiquitin Homeostasis Trigger Early Cholinergic Degeneration in Cellular and Animal AD-Model
Valentina Latina, Silvia Caioli, Cristina Zona, Maria Teresa Ciotti, Antonella Borreca, Pietro Calissano, Giuseppina Amadoro
in Frontiers in Cellular Neuroscience | New and Recent Articles on December 13, 2018 06:00 AM.
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Manganese-Enhanced Magnetic Resonance Imaging: Overview and Central Nervous System Applications With a Focus on Neurodegeneration
Ryan A. Cloyd, Shon A. Koren, Jose F. Abisambra
in Frontiers in Aging Neuroscience | New and Recent Articles on December 13, 2018 06:00 AM.
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Persistent Neuroadaptations in the Expression of Genes Involved in Cholesterol Homeostasis Induced by Chronic, Voluntary Alcohol Intake in Rats
Josette Alsebaaly, Emilie Dugast, Laure Favot, Lydia Rabbaa Khabbaz, Marcello Solinas, Nathalie Thiriet
in Frontiers in Molecular Neuroscience | New and Recent Articles on December 13, 2018 06:00 AM.
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Increasing Human Performance by Sharing Cognitive Load Using Brain-to-Brain Interface
Vladimir A. Maksimenko, Alexander E. Hramov, Nikita S. Frolov, Annika Lüttjohann, Vladimir O. Nedaivozov, Vadim V. Grubov, Anastasia E. Runnova, Vladimir V. Makarov, Jürgen Kurths, Alexander N. Pisarchik
in Frontiers in Neuroscience | Neural Technology section | New and Recent Articles on December 13, 2018 06:00 AM.
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Systems Biology Understanding of the Effects of Lithium on Affective and Neurodegenerative Disorders
Weihao Ge, Eric Jakobsson
in Frontiers in Neuroscience | Neurodegeneration section | New and Recent Articles on December 13, 2018 06:00 AM.
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Tuning Neuromodulation Effects by Orientation Selective Deep Brain Stimulation in the Rat Medial Frontal Cortex
Lauri J. Lehto, Pavel Filip, Hanne Laakso, Alejandra Sierra, Julia P. Slopsema, Matthew D. Johnson, Lynn E. Eberly, Walter C. Low, Olli Gröhn, Heikki Tanila, Silvia Mangia, Shalom Michaeli
in Frontiers in Neuroscience | Brain Imaging Methods section | New and Recent Articles on December 13, 2018 06:00 AM.
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Bayesian deep neural networks for low-cost neurophysiological markers of Alzheimer's disease severity. (arXiv:1812.04994v2 [stat.ML] UPDATED)

As societies around the world are ageing, the number of Alzheimer's disease (AD) patients is rapidly increasing. To date, no low-cost, non-invasive biomarkers have been established to advance the objectivization of AD diagnosis and progression assessment. Here, we utilize Bayesian neural networks to develop a multivariate predictor for AD severity using a wide range of quantitative EEG (QEEG) markers. The Bayesian treatment of neural networks both automatically controls model complexity and provides a predictive distribution over the target function, giving uncertainty bounds for our regression task. It is therefore well suited to clinical neuroscience, where data sets are typically sparse and practitioners require a precise assessment of the predictive uncertainty. We use data of one of the largest prospective AD EEG trials ever conducted to demonstrate the potential of Bayesian deep learning in this domain, while comparing two distinct Bayesian neural network approaches, i.e., Monte Carlo dropout and Hamiltonian Monte Carlo.

in q-bio.NC updates on arXiv.org on December 13, 2018 01:30 AM.
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Real-time cortical simulations - Energy and interconnect scaling on distributed systems. (arXiv:1812.04974v1 [cs.DC])

We profile the impact of computation and inter-processor communication on the energy consumption and on the scaling of cortical simulations approaching the real-time regime on distributed computing platforms. Also, the speed and energy consumption of processor architectures typical of standard HPC and embedded platforms are compared. We demonstrate the importance of the design of low-latency interconnect for speed and energy consumption. The cost of cortical simulations is quantified using the Joule per synaptic event metric on both architectures. Reaching efficient real-time on large scale cortical simulations is of increasing relevance for both future bio-inspired artificial intelligence applications and for understanding the cognitive functions of the brain, a scientific quest that will require to embed large scale simulations into highly complex virtual or real worlds. This work stands at the crossroads between the WaveScalES experiment in the Human Brain Project (HBP), which includes the objective of large scale thalamo-cortical simulations of brain states and their transitions, and the ExaNeSt and EuroExa projects, that investigate the design of an ARM-based, low-power High Performance Computing (HPC) architecture with a dedicated interconnect scalable to million of cores; simulation of deep sleep Slow Wave Activity (SWA) and Asynchronous aWake (AW) regimes expressed by thalamo-cortical models are among their benchmarks.

in q-bio.NC updates on arXiv.org on December 13, 2018 01:30 AM.
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Experimental Comparison of Hardware-Amenable Spike Detection Algorithms for iBMIs. (arXiv:1812.04786v1 [q-bio.NC])

This paper presents an experiment based comparison of absolute threshold (AT) and non-linear energy operator (NEO) spike detection algorithms in Intra-cortical Brain Machine Interfaces (iBMIs). Results show an average increase in decoding performance of approx. 5% in monkey A across 28 sessions recorded over 6 days and approx. 2% in monkey B across 35 sessions recorded over 8 days when using NEO over AT. To the best of our knowledge, this is the first ever reported comparison of spike detection algorithms in an iBMI experimental framework involving two monkeys. Based on the improvements observed in an experimental setting backed by previously reported improvements in simulation studies, we advocate switching from state of the art spike detection technique - AT to NEO.

in q-bio.NC updates on arXiv.org on December 13, 2018 01:30 AM.
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Designing Artificial Cognitive Architectures: Brain Inspired or Biologically Inspired?. (arXiv:1812.04769v1 [cs.AI])

Artificial Neural Networks (ANNs) were devised as a tool for Artificial Intelligence design implementations. However, it was soon became obvious that they are unable to fulfill their duties. The fully autonomous way of ANNs working, precluded from any human intervention or supervision, deprived of any theoretical underpinning, leads to a strange state of affairs, when ANN designers cannot explain why and how they achieve their amazing and remarkable results. Therefore, contemporary Artificial Intelligence R&D looks more like a Modern Alchemy enterprise rather than a respected scientific or technological undertaking. On the other hand, modern biological science posits that intelligence can be distinguished not only in human brains. Intelligence today is considered as a fundamental property of each and every living being. Therefore, lower simplified forms of natural intelligence are more suitable for investigation and further replication in artificial cognitive architectures.

in q-bio.NC updates on arXiv.org on December 13, 2018 01:30 AM.
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Impact of Intervals on the Emotional Effect in Western Music. (arXiv:1812.04723v1 [q-bio.NC])

Every art form ultimately aims to invoke an emotional response over the audience, and music is no different. While the precise perception of music is a highly subjective topic, there is an agreement in the "feeling" of a piece of music in broad terms. Based on this observation, in this study, we aimed to determine the emotional feeling associated with short passages of music; specifically by analyzing the melodic aspects. We have used the dataset put together by Eerola et. al. which is comprised of labeled short passages of film music. Our initial survey of the dataset indicated that other than "happy" and "sad" labels do not possess a melodic structure. We transcribed the main melody of the happy and sad tracks and used the intervals between the notes to classify them. Our experiments have shown that treating a melody as a bag-of-intervals do not possess any predictive power whatsoever, whereas counting intervals with respect to the key of the melody yielded a classifier with 85% accuracy.

in q-bio.NC updates on arXiv.org on December 13, 2018 01:30 AM.
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The neurobiological basis of narcolepsy

The neurobiological basis of narcolepsy
The neurobiological basis of narcolepsy, Published online: 13 December 2018; doi:10.1038/s41583-018-0097-x
Narcolepsy is a sleep disorder caused by selective loss of orexin-producing neurons. Scammell and colleagues describe the functions of orexin neurons and the effects of their loss and review evidence implicating the immune system in the pathogenesis of the disorder.
in Nature Reviews Neuroscience - Issue - nature.com science feeds on December 13, 2018 12:00 AM.
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Author Correction: Epigenetic regulation in psychiatric disorders

Author Correction: Epigenetic regulation in psychiatric disorders
Author Correction: Epigenetic regulation in psychiatric disorders, Published online: 13 December 2018; doi:10.1038/s41583-018-0089-x
Author Correction: Epigenetic regulation in psychiatric disorders
in Nature Reviews Neuroscience - Issue - nature.com science feeds on December 13, 2018 12:00 AM.
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Meiotic drive of female-inherited supernumerary chromosomes in a pathogenic fungus
Meiosis is a key cellular process of sexual reproduction involving the pairing of homologous sequences. In many species however, meiosis can also involve the segregation of supernumerary chromosomes, which can lack a homolog. How these unpaired chromosomes undergo meiosis is largely unknown. In this study we investigated chromosome segregation during meiosis in the haploid fungus Zymoseptoria tritici that possesses a large complement of supernumerary chromosomes. We used isogenic whole chromosome deletion strains to compare meiotic transmission of chromosomes when paired and unpaired. Unpaired chromosomes inherited from the male parent as well as paired supernumerary chromosomes in general showed Mendelian inheritance. In contrast, unpaired chromosomes inherited from the female parent showed non-Mendelian inheritance but were amplified and transmitted to all meiotic products. We concluded that the supernumerary chromosomes of Z. tritici show a meiotic drive and propose an additional feedback mechanism during meiosis which initiates amplification of unpaired female-inherited chromosomes.
in eLife: latest articles on December 13, 2018 12:00 AM.
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Structured illumination microscopy combined with machine learning for the high throughput analysis of virus structure
Optical super-resolution microscopy techniques enable high molecular specificity with high spatial resolution and constitute a set of powerful tools in the investigation of the structure of supramolecular assemblies such as viruses. Here, we report on a new methodology which combines Structured Illumination Microscopy (SIM) with machine learning algorithms to image and classify the structure of large populations of biopharmaceutical viruses with high resolution. The method offers information on virus morphology that can ultimately be linked with functional performance. We demonstrate the approach on viruses produced for oncolytic viriotherapy (Newcastle Disease Virus) and vaccine development (Influenza). This unique tool enables the rapid assessment of the quality of viral production with high throughput obviating the need for traditional batch testing methods which are complex and time consuming. We show that our method also works on non-purified samples from pooled harvest fluids directly from the production line.
in eLife: latest articles on December 13, 2018 12:00 AM.
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miR-34a is a microRNA safeguard for Citrobacter-induced inflammatory colon oncogenesis
Inflammation often induces regeneration to repair the tissue damage. However, chronic inflammation can transform temporary hyperplasia into a fertile ground for tumorigenesis. Here, we demonstrate that the microRNA miR-34a acts as a central safeguard to protect the inflammatory stem cell niche and reparative regeneration. Although playing little role in regular homeostasis, miR-34a deficiency leads to colon tumorigenesis after Citrobacter rodentium infection. miR-34a targets both immune and epithelial cells to restrain inflammation-induced stem cell proliferation. miR-34a targets Interleukin 6 receptor (IL-6R) and Interleukin 23 receptor (IL-23R) to suppress T helper 17 (Th17) cell differentiation and expansion, targets chemokine CCL22 to hinder Th17 cell recruitment to the colon epithelium, and targets an orphan receptor Interleukin 17 receptor D (IL-17RD) to inhibit IL-17 induced stem cell proliferation. Our study highlights the importance of microRNAs in protecting the stem cell niche during inflammation despite their lack of function in regular tissue homeostasis.
in eLife: latest articles on December 13, 2018 12:00 AM.
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Gene flow mediates the role of sex chromosome meiotic drive during complex speciation
During speciation, sex chromosomes often accumulate interspecific genetic incompatibilities faster than the rest of the genome. The drive theory posits that sex chromosomes are susceptible to recurrent bouts of meiotic drive and suppression, causing the evolutionary build-up of divergent cryptic sex-linked drive systems and, incidentally, genetic incompatibilities. To assess the role of drive during speciation, we combine high-resolution genetic mapping of X-linked hybrid male sterility with population genomics analyses of divergence and recent gene flow between the fruitfly species, Drosophila mauritiana and D. simulans. Our findings reveal a high density of genetic incompatibilities and a corresponding dearth of gene flow on the X chromosome. Surprisingly, we find that a known drive element recently migrated between species and, rather than contributing to interspecific divergence, caused a strong reduction in local sequence divergence, undermining the evolution of hybrid sterility. Gene flow can therefore mediate the effects of selfish genetic elements during speciation.
in eLife: latest articles on December 13, 2018 12:00 AM.
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Target-detecting neurons in the dragonfly lock on to selectively attended targets
The visual world projects a complex and rapidly changing image on to the retina, presenting a computational challenge for any animal relying on vision for an accurate view of the world. One such challenge is parsing a visual scene for the most salient targets, such as the selection of prey amidst a swarm. The ability to selectivity prioritize processing of some stimuli over others is known as selective attention. Previously, we identified a dragonfly visual neuron called Centrifugal Small Target Motion Detector 1 (CSTMD1) that exhibits selective attention when presented with multiple, equally salient features. Here we conducted electrophysiological recordings from CSTMD1 neurons in vivo, whilst presenting visual stimuli on a monitor display. To identify the target selected in any given trial, we modulated the intensity of moving targets, each with a unique frequency (frequency-tagging). We find that the frequency information of the selected stimulus is preserved in the neuronal response, whilst the distracter is completely ignored. We show that the competitive system that underlies selection in this neuron can be biased by the presentation of a preceding target on the same trajectory, even when it is of lower contrast to the distracter. With an improved method of identifying and biasing target selection in CSTMD1, the dragonfly provides an effective animal model system to probe the mechanisms underlying neuronal selective attention.
in bioRxiv Subject Collection: Neuroscience on December 13, 2018 12:00 AM.
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Using neural distance to predict reaction time for categorizing the animacy, shape, and abstract properties of objects
A large number of neuroimaging studies have shown that information about object category can be decoded from regions of the ventral visual pathway. One question is how this information might be functionally exploited in the brain. In an attempt to answer this question, some studies have adopted a neural distance-to-bound approach, and shown that distance to a classifier decision boundary through neural activation space can be used to predict reaction times (RT) on animacy categorization tasks. However, these experiments have not controlled for possible visual confounds, such as shape, in their stimulus design. In the present study we sought to determine whether, when animacy and shape properties are orthogonal, neural distance in low- and high-level visual cortex would predict categorization RTs. We also investigated whether a combination of animacy and shape distance might predict RTs when categories crisscrossed the two stimulus dimensions, and so were not linearly separable. In line with previous results, we found that RTs correlated with neural distance, but only for animate stimuli, with similar, though weaker, asymmetric effects for the shape and crisscrossing tasks. Taken together, these results suggest there is potential to expand the neural distance-to-bound approach to other divisions beyond animacy and object category.
in bioRxiv Subject Collection: Neuroscience on December 13, 2018 12:00 AM.
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Electron cryo-tomography of vestibular hair-cell stereocilia
High-resolution imaging of hair-cell stereocilia of the inner ear has contributed substantially to our understanding of auditory and vestibular function. To provide three-dimensional views of the structure of stereocilia cytoskeleton and membranes, we developed a method for rapidly freezing unfixed stereocilia on electron microscopy grids, which allowed subsequent 3D imaging by electron cryo-tomography. Structures of stereocilia tips, shafts, and tapers were revealed, demonstrating that the actin paracrystal was not perfectly ordered. This sample-preparation and imaging procedure will allow for examination of structural features of stereocilia in a near-native state.
in bioRxiv Subject Collection: Neuroscience on December 13, 2018 12:00 AM.
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Salience Network Disruption in US Army Soldiers with PTSD
BACKGROUND: Better understanding of the neurobiology of posttraumatic stress disorder (PTSD) may be critical to developing novel, effective therapeutics. Here, we conducted a data-driven investigation using a well-established, graph- based topological measure of nodal strength to determine the extent of functional dysconnectivity in a cohort of active duty US Army soldiers with PTSD compared to controls. METHODS: 102 participants with (n=50) or without PTSD (n=52) completed functional magnetic resonance imaging (fMRI) at rest and during symptom provocation using subject-specific script imagery. Vertex/voxel global brain connectivity with global signal regression (GBCr), a measure of nodal strength, was calculated as the average of its functional connectivity with all other vertices/voxels in the brain gray matter. RESULTS: In contrast to during resting-state, where there were no group differences, we found a significantly higher GBCr, in PTSD participants compared to controls, in areas within the right hemisphere, including anterior insula, caudal- ventrolateral prefrontal, and rostral-ventrolateral parietal cortices. Overall, these clusters overlapped with the ventral and dorsal salience networks. Post hoc analysis showed increased GBCr in these salience clusters during symptom provocation compared to resting-state. In addition, resting-state GBCr in the salience clusters predicted GBCr during symptom provocation in PTSD participants but not in controls. CONCLUSION: In PTSD, increased connectivity within the salience network has been previously hypothesized, based primarily on seed-based connectivity findings. The current results strongly support this hypothesis using whole-brain network measure in a fully data-driven approach. It remains to be seen in future studies whether these identified salience disturbances would normalize following treatment.
in bioRxiv Subject Collection: Neuroscience on December 13, 2018 12:00 AM.
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Inference of Nonlinear Spatial Subunits by Spike-Triggered Clustering in Primate Retina
Integration of rectified synaptic inputs is a widespread nonlinear motif in sensory neuroscience. We present a novel method for maximum likelihood estimation of nonlinear subunits by soft-clustering spike-triggered stimuli. Subunits estimated from parasol ganglion cells recorded in macaque retina partitioned the receptive field into compact regions, likely representing bipolar cell inputs. Joint clustering with multiple RGCs revealed shared subunits in neighboring cells, producing a parsimonious population model. Closed-loop subunit validation was then performed by projecting white noise into the null space of the linear receptive field. Responses to these null stimuli were more accurately explained by a model with multiple subunits, and were stronger in OFF cells than ON cells. Presentation of natural stimuli containing jittering edges and textures also revealed greater response prediction accuracy with the subunit model. Finally, the generality of the approach was demonstrated by application to V1 data.
in bioRxiv Subject Collection: Neuroscience on December 13, 2018 12:00 AM.
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Distinct ipRGC subpopulations mediate light\'s acute and circadian effects on body temperature and sleep
The light environment greatly impacts human alertness, mood, and cognition by acute regulation of physiology and indirect alignment of circadian rhythms. Both processes require the melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs), but the relevant downstream brain areas remain elusive. ipRGCs project widely in the brain, including to the central circadian pacemaker, the suprachiasmatic nucleus (SCN). Here we show that body temperature and sleep responses to light are absent after genetic ablation of all ipRGCs except a subpopulation that projects to the SCN. Furthermore, by chemogenetic activation of the ipRGCs that avoid the SCN, we show that these cells are sufficient for acute changes in body temperature. Our results challenge the idea that the SCN is a major relay for the acute effects of light on non-image forming behaviors and identify the sensory cells that initiate light's profound effects on body temperature and sleep.
in bioRxiv Subject Collection: Neuroscience on December 13, 2018 12:00 AM.
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In trans variant calling reveals enrichment for compound heterozygous variants in genes involved in neuronal development and growth.
Compound heterozygotes occur when different mutations at the same locus on both maternal and paternal chromosomes produce a recessive trait. Here we present the tool VarCount for the quantification of mutations at the individual level. We used VarCount to characterize compound heterozygous coding variants in patients with epileptic encephalopathy and in the 1000 genomes participants. The Epi4k data contains variants identified by whole exome sequencing in patients with either Lennox-Gastaut Syndrome (LGS) or Infantile Spasms (IS), as well as their parents. We queried the Epi4k dataset (264 trios) and the phased 1000 genomes data (2504 participants) for recessive variants. To assess enrichment, transcript counts were compared between the Epi4k and 1000 genomes participants using minor allele frequency (MAF) cutoffs of 0.5% and 1.0%, and including all ancestries or only probands of European ancestry. In the Epi4k participants, we found enrichment for rare, compound heterozygous mutations in six genes, including three involved in neuronal growth and development; PRTG (p=0.00086, 1% MAF, combined ancestries), TNC (p=0.0221% MAF, combined ancestries), and MACF1 (p=0.0245, 0.5% MAF, EU ancestry). Due the total number of transcripts considered in these analyses, the enrichment detected was not significant after correction for multiple testing and higher powered or prospective studies are necessary to validate the candidacy of these genes. However, PRTG, TNC, and MACF1 are potential novel recessive epilepsy genes and our results highlight that compound heterozygous mutations should be considered in sporadic epilepsy.
in bioRxiv Subject Collection: Neuroscience on December 13, 2018 12:00 AM.
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Not Just A Number: Age-Related Modulations of Oscillatory Patterns Underlying Top-Down and Bottom-Up Attention.
Attention operates through top-down (TD) and bottom-up (BU) mechanisms. Recently, it has been suggested that these mechanisms are supported by distinct frequency bands with slower (alpha) frequencies indexing facilitatory and suppressive mechanisms of TD attention and faster (gamma) frequencies indexing BU attentional capture. Ageing is characterized by increased behavioral distractibility, which can result from either a reduced efficiency of TD attention, or an enhanced triggering of BU attention. However, only few studies have investigated the impact of ageing on the balance between TD and BU attention and its oscillatory correlates. MEG data were collected from 14 elderly (mean age = 67) and 14 matched young (mean age = 25) healthy human participants while performing a modified version of the Competitive Attention Task with pitch discrimination. TD attention was manipulated by a visual cue that was either informative or not of the side of the monaural target sound. BU attention was triggered by binaural distracting sounds that were played (25% of trials) between the cue and the target. Behaviorally, older participants displayed an exacerbated distractibility to late distractors. Electrophysiologically, in comparison to young participants, they exhibited (1) deficits in the suppressive mechanisms of TD attention, indexed by a reduced alpha synchronization in task-irrelevant visual regions, (2) less prominent alpha peak-frequency differences between cortical regions, (3) a similar BU system activation indexed by distractor-induced gamma responses, and (4) a reduced activation of prefrontal inhibitory control regions. These results show that the ageing-related increased distractibility is of TD origin.
in bioRxiv Subject Collection: Neuroscience on December 13, 2018 12:00 AM.
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The time course of recognition memory impairment and glial pathology in the hAPP-J20 mouse model of Alzheimer\'s disease.
The role of cellular changes in the neurovascular unit is increasingly being investigated to understand the pathogenesis of Alzheimers disease. The aim of the current study was to determine the time course of recognition memory impairment in the J20 mouse model of AD, in relation to neuroinflammatory responses and the pathology of A{beta}. Male hAPP-J20 and wild-type mice were assessed at 3, 6, 9, and 12 months of age. The spontaneous object recognition (SOR) task provided a measure of memory, with assessment of both a short delay (1 min) and a long delay (4 hrs). Immunohistochemistry was used to characterise A{beta}-deposition, and quantify astrocyte and microglial responses. At all ages tested J20 mice had impaired long-term, but preserved short-term, recognition memory. Wild-types demonstrated preserved long-term memory up to 9 months of age, and preserved short-term memory at all ages tested. Plaque pathology in the J20 mice was present from 6 months onwards, with co-localisation of reactive microglia and activated astrocytes. Reactive microglia and astrocyte activation in the hippocampus were significantly greater in the J20 mice at 9 months, compared to wild-types. This study contributes to our understanding of the pathological and cognitive mechanisms at play in AD. J20 mice showed impairment in retaining information over longer periods from an early age, preceding the deposition of A{beta} and glial activation. Defining early physiological changes in relation to cognitive decline could provide insight into new therapeutic targets early in the disease process, when intervention is most likely to effectively slow disease progression.
in bioRxiv Subject Collection: Neuroscience on December 13, 2018 12:00 AM.
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Neural activity in a hippocampus-like region of the teleost pallium are associated with navigation and active sensing
Neural mechanisms underlying spatial navigation in fish are unknown and little is known, for any vertebrate, about the relationship between active sensing and the formation of spatial maps. The weakly electric fish, Gymnotus Carapo, uses their active electric sense for spatial navigation. The electric organ discharge rate (EODr) undergoes transient increases during navigation to enhance electrosensory sampling. Gymnotus also uses stereotyped forward/backward swimming as a second form of active sensing that brings objects towards the electroreceptor-dense head region. We wirelessly recorded neural activity from the pallium of freely swimming Gymnotus. Spiking activity was sparse and occurred only during swimming. Notably, some units exhibited significant place specificity and/or association with both forms of active sensing. Our results provide the first characterization of neural activity in a hippocampal-like region of a teleost fish brain and connects active sensing via sensory sampling rate and directed movements to higher order encoding of spatial information.
in bioRxiv Subject Collection: Neuroscience on December 13, 2018 12:00 AM.
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Differentiation of mild cognitive impairment using an entorhinal cortex-based test of VR navigation
The entorhinal cortex is one of the first regions to exhibit neurodegeneration in Alzheimer's disease, and as such identification of entorhinal cortex dysfunction may aid detection of the disease in its earliest stages. Extensive evidence demonstrates that the entorhinal cortex is critically implicated in navigation underpinned by the firing of spatially modulated neurons. This study tested the hypothesis that entorhinal-dependent navigation is impaired in pre-dementia Alzheimer's disease. Forty-five patients with mild cognitive impairment (26 with CSF Alzheimer's disease biomarker data: 12 biomarker-positive and 14 biomarker-negative) and 41 healthy control participants undertook an immersive virtual reality path integration test, as a measure of entorhinal-dependent navigation. Behavioural performance was correlated with MRI measures of entorhinal cortex volume, and the classification accuracy of the path integration task was compared with a battery of cognitive tests considered sensitive and specific for early Alzheimer's Disease. Biomarker-positive patients exhibited larger errors in the navigation task than biomarker-negative patients, whose performance did not significantly differ from controls participants. Path-integration errors were negatively correlated with the volumes of the total entorhinal cortex and of its posteromedial subdivision. The path integration task demonstrated higher diagnostic sensitivity and specificity for differentiating biomarker positive versus negative patients (area under the curve = 0.90) than was achieved by the best of the cognitive tests (area under the curve = 0.57). This study demonstrates that an entorhinal cortex-based virtual reality navigation task can differentiate patients with mild cognitive impairment at low and high risk of developing dementia, with classification accuracy superior to reference cognitive tests considered to be highly sensitive to early Alzheimer's disease. This study provides evidence that navigation tasks may aid early diagnosis of Alzheimer's disease, and the basis of this in animal cellular and behavioural studies provides the opportunity to answer the unmet need for translatable outcome measures for comparing treatment effect across preclinical and clinical trial phases of future anti-Alzheimer's drugs.
in bioRxiv Subject Collection: Neuroscience on December 13, 2018 12:00 AM.
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Automated Seizure Detection Tailored Towards Portable Patient Care Using A Novel, Computationally Efficient Method of Analysis
Epilepsy is a devastating neurological disorder that affects approximately 1-3% population worldwide. Wearables have recently gained more popularity as having a promising future in epilepsy management including seizure alert and close-loop therapy for severe forms of seizures. Due to the random and low frequency of seizures, seizure evaluation requires continuous, long-term EEG monitoring, which produces a large volume of data. The future treatment systems will rely on algorithms that can detect seizures with high precision and low computational cost. Previous implemented algorithms have used various computationally expensive methods of data transformation and feature extraction. In the present study, we developed a new computationally efficient seizure detection algorithm based on analysis of the broad, global shape EEG data of tonic-clonic seizures from a mouse model of temporal lobe epilepsy (TLE). To perform this algorithm, EEG data was normalized and processed through a rolling mean function, producing smoothed, simplified EEG clips that represent the global shape of the clip. These signals were then directly inputted for SVM training and testing. This novel method of seizure analysis only requires a small fraction of EEG data points, yet achieved an accuracy rate of approximately 98.51%. Our study provides a proof of principle that this simpler method could have an advantage in low-power platform such as wearables. Recently, the FDA approved a seizure detection app called embrace2 by Empatica. However, their algorithm detects seizures indirectly by monitoring heart rate and muscle contractions. Our novel algorithm detects seizures directly through analysis of brain activity. Thus, our algorithm may be better suited for future wearables in epilepsy management.
in bioRxiv Subject Collection: Neuroscience on December 13, 2018 12:00 AM.
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Characterization of young and old adult brains: An EEG functional connectivity analysis
Brain connectivity studies have reported that functional networks change with older age. We aim to (1) investigate whether electroencephalography (EEG) data can be used to distinguish between individual functional networks of young and old adults; and (2) identify the functional connections that contribute to this classification. Two eyes-open resting-state EEG recording sessions with 64 electrodes for each of 22 younger adults (19-37 years) and 22 older adults (63-85 years) were conducted. For each session, imaginary coherence matrices in theta, alpha, beta and gamma bands were computed. A range of machine learning classification methods were utilized to distinguish younger and older adult brains. A support vector machine (SVM) classifier was 94% accurate in classifying the brains by age group. We report decreased functional connectivity with older age in theta, alpha and gamma bands, and increased connectivity with older age in beta band. Most connections involving frontal, temporal, and parietal electrodes, and approximately two-thirds of connections involving occipital electrodes, showed decreased connectivity with older age. Just over half of the connections involving central electrodes showed increased connectivity with older age. Functional connections showing decreased strength with older age had significantly longer electrode-to-electrode distance than those that increased with older age. Most of the connections used by the classifier to distinguish participants by age group belonged to the alpha band. Findings suggest a decrease in connectivity in key networks and frequency bands associated with attention and awareness, and an increase in connectivity of the sensorimotor functional networks with ageing during a resting state.
in bioRxiv Subject Collection: Neuroscience on December 13, 2018 12:00 AM.
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CHANCE: a method that enables a researcher to fully know the content of consciousness of a subject in scientific experiments
The content of consciousness (cC) constitutes an essential part of our human life and the very heart of the hard problem of consciousness. In science, the cC of a subject (participant) has been examined indirectly through measuring his/her behavioral reports, bodily signs, or neural signals. None of them, however, reflects the full spectrum of the subject's cC, hampering a researcher to fully know the subject's cC and find its neural basis precisely and extensively. Here we propose a method, termed CHANCE that enables a researcher to experience and know directly the full spectrum of the subject's cC in scientific experiments. The degree of epistemic objectivity of a specific entity has been reasonably judged by relevant individuals who have the ability to judge the faithfulness of the entity to the truth (the true facts). More number of relevant individuals who judge the entity as the truth results in more objectivity of the entity epistemically. Thus, even the knowledge of a specific cC itself would be regarded as epistemically objective if it was judged as the truth (being truly had) by multiple relevant individuals. We propose CHANCE consisting of three empirical steps to change the knowledge of the cC itself from epistemically subjective to objective: (1) finding a minimally-sufficient content-knowledge-specific neural correlates of consciousness (msckNCC), and (2) selecting an msckNCC that produces the knowledge of only one specific cC but not others, and finally, (3) among the msckNCCs that verified the 2nd step, selecting an msckNCC that is reproducible in multiple brains.
in bioRxiv Subject Collection: Neuroscience on December 13, 2018 12:00 AM.
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Engagement of Pulvino-cortical Feedforward and Feedback Pathways in Cognitive Computations
Very little is known about the function of the thalamus beyond relaying sensory information to the cortex. Jaramillo et al. present a biologically based model of pulvino-cortical interactions and provide a unified account of the pulvinar’s computational role across cognitive tasks.
in Neuron on December 12, 2018 06:00 PM.
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A Computational Model of Dual Competition between the Basal Ganglia and the Cortex
Abstract
We propose a model that includes interactions between the cortex, the basal ganglia and the thalamus based on a dual competition. We hypothesize that the striatum, the subthalamic nucleus, the internal pallidum (GPi), the thalamus, and the cortex are involved in closed feedback loops through the hyperdirect and direct pathways. These loops support a competition process that results in the ability of basal ganglia to make a cognitive decision followed by a motor one. Considering lateral cortical interactions, another competition takes place inside the cortex allowing the latter to make a cognitive and a motor decision. We show how this dual competition endows the model with two regimes. One is driven by reinforcement learning, the other by Hebbian learning. The final decision is made according to a combination of these two mechanisms with a gradual transfer from the former to the latter. We confirmed these theoretical results on primates (Macaca mulata) using a novel paradigm predicted by the model.
Significance statement In this article, we propose a detailed computational model of interaction between basal ganglia and cortex in which, the former adapts its response according to the outcome while the latter is insensitive to it. The model shows how these two processes interact in order to issue a unique behavioral answer. This prediction has been verified on monkeys, demonstrating how these two processes are both competing (expression) and cooperating (learning). These results suggest that a behavioral decision emerges actually from a dual competition of two distinct but entangled systems.

in RSS PAP on December 12, 2018 05:37 PM.
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Nociceptin/Orphanin-FQ inhibits gonadotropin releasing hormone neurons via G-protein gated inwardly rectifying potassium channels
Abstract
The pulsatile release of gonadotrophin releasing hormone (GnRH) is a key feature of the hypothalamic-pituitary-gonadal axis. Kisspeptin neurons in the arcuate nucleus (ARC) trigger GnRH neuronal activity, but how GnRH neurons return to baseline electrical activity is unknown. Nociceptin/orphanin-FQ (OFQ) is an inhibitory neuromodulator. ARC Proopiomelanocortin (POMC) neurons, known to receive inputs from ARC kisspeptin neurons, contact GnRH neurons and coexpress OFQ in rat. In the present study, the effect of OFQ(1-13) on GnRH neurons was determined in mouse. We identified transcripts for the OFQ receptor (opioid receptor like 1, ORL1) in GnRH neurons and, using two model systems (explants and slices), found that OFQ exerted a potent inhibition on GnRH neurons, with or without excitatory inputs. We confirmed the inhibition was mediated by ORL1 via G_i/o protein coupling. The inhibition, occurring independently of levels of intracellular cyclic adenosine monophosphate, was sensitive to inwardly rectifying potassium channels. The only specific blocker of G_i/o protein-coupled inwardly-rectifying potassium (GIRK) channels, tertiapin-Q (TPNQ), was ineffective on the OFQ inhibition. Two GIRK activators, one sharing the binding site of TPNQ and one active only on GIRK1-containing GIRK channels, failed to trigger an inhibition. In contrast, protein kinase C phosphorylation activation known to inhibit GIRK2-mediated currents prevented the OFQ inhibition. These results indicate a specific combination of GIRK subunits, GIRK2/3 in GnRH neurons. In vivo, double labeled OFQ/POMC fibers were found in the vicinity of GnRH neurons and OFQ fibers apposed GnRH neurons. Together, this study brings into light a potent neuromodulator of GnRH neurons.
Significance Statement Fertility is controlled centrally by neurons secreting gonadotrophin releasing hormone (GnRH) and critically relies on their pulsatile secretory profile. GnRH pulses depend on kisspeptin neurons located in the arcuate nucleus (ARC). However, kisspeptin provides a long-lasting stimulation and how GnRH neurons return to baseline electrical activity is unknown. Here, we show nociceptin/orphanin-FQ (OFQ) potently inhibits GnRH neurons. The signaling pathway involves the receptor, opioid receptor like 1, and downstream effectors G_i/o protein and G_i/o protein-coupled inwardly-rectifying potassium (GIRK) channels. Notably, the GIRK channels in GnRH neurons exhibit a specific subunit composition, GIRK2/3. Together, these data identify a new messenger in modulating reproductive function.

in RSS PAP on December 12, 2018 05:37 PM.
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Motion discrimination and the motion aftereffect in mouse vision
Abstract
Prolonged exposure to motion in one direction often leads to the illusion of motion in the opposite direction for stationary objects. This motion aftereffect likely arises across several visual areas from adaptive changes in the balance of activity and competitive interactions. We examined whether or not the mouse was susceptible to this same illusion to determine whether it would be a suitable model for learning about the neural representation of the motion aftereffect. Under a classical conditioning paradigm, mice learned to lick when presented with motion in one direction and not the opposite direction. When the mice were adapted to motion preceding this test, their lick behavior for zero coherence motion was biased for motion in the opposite direction of the adapting stimulus. Overall, lick count versus motion coherence shifted in the opposite direction of the adapting stimulus. This suggests that although the mouse has a simpler visual system compared to primates, it still is subject to the motion aftereffect and may elucidate the underlying circuitry.
Significance Statement The motion aftereffect is a well-known illusion that provides insight about motion processing and adaptation throughout the visual system. We demonstrate that motion discrimination in mice is affected by extended viewing of coherent motion, in a manner consistent with the effects reported in primates. The mouse model currently offers unprecedented experimental tools for studying neural circuitry and our results support the mouse as a model to study this phenomenon.

in RSS PAP on December 12, 2018 05:37 PM.
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This Week in The Journal

in Journal of Neuroscience current issue on December 12, 2018 05:30 PM.
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Acknowledgment of Reviewers 2018

in Journal of Neuroscience current issue on December 12, 2018 05:30 PM.
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Collaborating Reviewers

in Journal of Neuroscience current issue on December 12, 2018 05:30 PM.
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Outstanding Reviewers 2018

in Journal of Neuroscience current issue on December 12, 2018 05:30 PM.
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Long-Lasting Electrophysiological After-Effects of High-Frequency Stimulation in the Globus Pallidus: Human and Rodent Slice Studies

Deep-brain stimulation (DBS) of the globus pallidus pars interna (GPi) is a highly effective therapy for movement disorders, yet its mechanism of action remains controversial. Inhibition of local neurons because of release of GABA from afferents to the GPi is a proposed mechanism in patients. Yet, high-frequency stimulation (HFS) produces prolonged membrane depolarization mediated by cholinergic neurotransmission in endopeduncular nucleus (EP, GPi equivalent in rodent) neurons. We applied HFS while recording neuronal firing from an adjacent electrode during microelectrode mapping of GPi in awake patients (both male and female) with Parkinson disease (PD) and dystonia. Aside from after-suppression and no change in neuronal firing, high-frequency microstimulation induced after-facilitation in 38% (26/69) of GPi neurons. In neurons displaying after-facilitation, 10 s HFS led to an immediate decrease of bursting in PD, but not dystonia patients. Moreover, the changes of bursting patterns in neurons with after-suppression or no change after HFS, were similar in both patient groups. To explore the mechanisms responsible, we applied HFS in EP brain slices from rats of either sex. As in humans, HFS in EP induced two subtypes of after-excitation: excitation or excitation with late inhibition. Pharmacological experiments determined that the excitation subtype, induced by lower charge density, was dependent on glutamatergic transmission. HFS with higher charge density induced excitation with late inhibition, which involved cholinergic modulation. Therefore HFS with different charge density may affect the local neurons through multiple synaptic mechanisms. The cholinergic system plays a role in mediating the after-facilitatory effects in GPi neurons, and because of their modulatory nature, may provide a basis for both the immediate and delayed effects of GPi-DBS. We propose a new model to explain the mechanisms of DBS in GPi.

SIGNIFICANCE STATEMENT Deep-brain stimulation (DBS) in the globus pallidus pars interna (GPi) improves Parkinson disease (PD) and dystonia, yet its mechanisms in GPi remain controversial. Inhibition has been previously described and thought to indicate activation of GABAergic synaptic terminals, which dominate in GPi. Here we report that 10 s high-frequency microstimulation induced after-facilitation of neural firing in a substantial proportion of GPi neurons in humans. The neurons with after-facilitation, also immediately reduced their bursting activities after high-frequency stimulation in PD, but not dystonia patients. Based on these data and further animal experiments, a mechanistic hypothesis involving glutamatergic, GABAergic, and cholinergic synaptic transmission is proposed to explain both short- and longer-term therapeutic effects of DBS in GPi.

in Journal of Neuroscience current issue on December 12, 2018 05:30 PM.
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Integration of Small- and Wide-Field Visual Features in Target-Selective Descending Neurons of both Predatory and Nonpredatory Dipterans

For many animals, target motion carries high ecological significance as this may be generated by a predator, prey, or potential mate. Indeed, animals whose survival depends on early target detection are often equipped with a sharply tuned visual system, yielding robust performance in challenging conditions. For example, many fast-flying insects use visual cues for identifying targets, such as prey (e.g., predatory dragonflies and robberflies) or conspecifics (e.g., nonpredatory hoverflies), and can often do so against self-generated background optic flow. Supporting these behaviors, the optic lobes of insects that pursue targets harbor neurons that respond robustly to the motion of small moving objects, even when displayed against syn-directional background clutter. However, in diptera, the encoding of target information by the descending neurons, which are more directly involved in generating the behavioral output, has received less attention. We characterized target-selective neurons by recording in the ventral nerve cord of male and female predatory Holcocephala fusca robberflies and of male nonpredatory Eristalis tenax hoverflies. We show that both species have dipteran target-selective descending neurons that only respond to target motion if the background is stationary or moving slowly, moves in the opposite direction, or has un-naturalistic spatial characteristics. The response to the target is suppressed when background and target move at similar velocities, which is strikingly different to the response of target neurons in the optic lobes. As the neurons we recorded from are premotor, our findings affect our interpretation of the neurophysiology underlying target-tracking behaviors.

SIGNIFICANCE STATEMENT Many animals use sensory cues to detect moving targets that may represent predators, prey, or conspecifics. For example, birds of prey show superb sensitivity to the motion of small prey, and intercept these at high speeds. In a similar manner, predatory insects visually track moving prey, often against cluttered backgrounds. Accompanying this behavior, the brains of insects that pursue targets contain neurons that respond exclusively to target motion. We here show that dipteran insects also have target-selective descending neurons in the part of their nervous system that corresponds to the vertebrate spinal cord. Surprisingly, and in contrast to the neurons in the brain, these premotor neurons are inhibited by background patterns moving in the same direction as the target.

in Journal of Neuroscience current issue on December 12, 2018 05:30 PM.
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Detailed Visual Cortical Responses Generated by Retinal Sheet Transplants in Rats with Severe Retinal Degeneration

To combat retinal degeneration, healthy fetal retinal sheets have been successfully transplanted into both rodent models and humans, with synaptic connectivity between transplant and degenerated host retina having been confirmed. In rodent studies, transplants have been shown to restore responses to flashes of light in a region of the superior colliculus corresponding to the location of the transplant in the host retina. To determine the quality and detail of visual information provided by the transplant, visual responsivity was studied here at the level of visual cortex where higher visual perception is processed. For our model, we used the transgenic Rho-S334ter line-3 rat (both sexes), which loses photoreceptors at an early age and is effectively blind at postnatal day 30. These rats received fetal retinal sheet transplants in one eye between 24 and 40 d of age. Three to 10 months following surgery, visually responsive neurons were found in regions of primary visual cortex matching the transplanted region of the retina that were as highly selective as normal rat to stimulus orientation, size, contrast, and spatial and temporal frequencies. Conversely, we found that selective response properties were largely absent in nontransplanted line-3 rats. Our data show that fetal retinal sheet transplants can result in remarkably normal visual function in visual cortex of rats with a degenerated host retina and represents a critical step toward developing an effective remedy for the visually impaired human population.

SIGNIFICANCE STATEMENT Age-related macular degeneration and retinitis pigmentosa lead to profound vision loss in millions of people worldwide. Many patients lose both retinal pigment epithelium and photoreceptors. Hence, there is a great demand for the development of efficient techniques that allow for long-term vision restoration. In this study, we transplanted dissected fetal retinal sheets, which can differentiate into photoreceptors and integrate with the host retina of rats with severe retinal degeneration. Remarkably, we show that transplants generated visual responses in cortex similar in quality to normal rats. Furthermore, transplants preserved connectivity within visual cortex and the retinal relay from the lateral geniculate nucleus to visual cortex, supporting their potential application in curing vision loss associated with retinal degeneration.

in Journal of Neuroscience current issue on December 12, 2018 05:30 PM.
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Membrane Potential Correlates of Network Decorrelation and Improved SNR by Cholinergic Activation in the Somatosensory Cortex

The nucleus basalis (NB) projects cholinergic axons to the cortex, where they play a major role in arousal, attention, and learning. Cholinergic inputs shift cortical dynamics from synchronous to asynchronous and improve the signal-to-noise ratio (SNR) of sensory responses. However, the underlying mechanisms of these changes remain unclear. Using simultaneous extracellular and whole-cell patch recordings in layer 4 of the mouse barrel cortex, we show that electrical or optogenetic activation of the cholinergic system has a differential effect on ongoing and sensory evoked activities. Cholinergic activation profoundly reduced the large spontaneous fluctuations in membrane potential and decorrelated ongoing activity. However, NB stimulation had no effect on the response to whisker stimulation or on signal correlations. These effects of cholinergic activation provide a unified explanation for the increased SNR of sensory response and for the reduction in noise correlations and explain the shift into the desynchronized cortical state, which are the hallmarks of arousal and attention.

SIGNIFICANCE STATEMENT Attention increases the signal-to-noise ratio (SNR) of cortical sensory response, which may reflect either reduction in background firing rate or increased sensory response. Extracellular recordings showed that attention also reduces the correlation in network activity. These effects are partially mediated by cholinergic axons from the nucleus basalis projecting to the entire cortex. To reveal the cellular and synaptic correlates of these cholinergic effects, we performed simultaneous intracellular and LFP recordings in the somatosensory cortex. Global or local cholinergic activation increased the SNR of sensory response mainly by reducing the rate and amplitude of background synaptic activity and also reduced network correlations. Therefore, coding of sensory information is enhanced by the cholinergic system mainly due to a reduction in spontaneous activity.

in Journal of Neuroscience current issue on December 12, 2018 05:30 PM.
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Characterization of Brain Dysfunction Induced by Bacterial Lipopeptides That Alter Neuronal Activity and Network in Rodent Brains

The immunopathological states of the brain induced by bacterial lipoproteins have been well characterized by using biochemical and histological assays. However, these studies have limitations in determining functional states of damaged brains involving aberrant synaptic activity and network, which makes it difficult to diagnose brain disorders during bacterial infection. To address this, we investigated the effect of Pam₃CSK₄ (PAM), a synthetic bacterial lipopeptide, on synaptic dysfunction of female mice brains and cultured neurons in parallel. Our functional brain imaging using PET with [¹⁸F]fluorodeoxyglucose and [¹⁸F] flumazenil revealed that the brain dysfunction induced by PAM is closely aligned to disruption of neurotransmitter-related neuronal activity and functional correlation in the region of the limbic system rather than to decrease of metabolic activity of neurons in the injection area. This finding was verified by in vivo tissue experiments that analyzed synaptic and dendritic alterations in the regions where PET imaging showed abnormal neuronal activity and network. Recording of synaptic activity also revealed that PAM reorganized synaptic distribution and decreased synaptic plasticity in hippocampus. Further study using in vitro neuron cultures demonstrated that PAM decreased the number of presynapses and the frequency of miniature EPSCs, which suggests PAM disrupts neuronal function by damaging presynapses exclusively. We also showed that PAM caused aggregation of synapses around dendrites, which may have caused no significant change in expression level of synaptic proteins, whereas synaptic number and function were impaired by PAM. Our findings could provide a useful guide for diagnosis and treatment of brain disorders specific to bacterial infection.

SIGNIFICANCE STATEMENT It is challenging to diagnose brain disorders caused by bacterial infection because neural damage induced by bacterial products involves nonspecific neurological symptoms, which is rarely detected by laboratory tests with low spatiotemporal resolution. To better understand brain pathology, it is essential to detect functional abnormalities of brain over time. To this end, we investigated characteristic patterns of altered neuronal integrity and functional correlation between various regions in mice brains injected with bacterial lipopeptides using PET with a goal to apply new findings to diagnosis of brain disorder specific to bacterial infection. In addition, we analyzed altered synaptic density and function using both in vivo and in vitro experimental models to understand how bacterial lipopeptides impair brain function and network.

in Journal of Neuroscience current issue on December 12, 2018 05:30 PM.
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Enhanced CRFR1-Dependent Regulation of a Ventral Tegmental Area to Prelimbic Cortex Projection Establishes Susceptibility to Stress-Induced Cocaine Seeking

The ability of stress to trigger cocaine seeking in humans and rodents is variable and is determined by the amount and pattern of prior drug use. This study examined the role of a corticotropin releasing factor (CRF)-regulated dopaminergic projection from the ventral tegmental area (VTA) to the prelimbic cortex in shock-induced cocaine seeking and its recruitment under self-administration conditions that establish relapse vulnerability. Male rats with a history of daily long-access (LgA; 14 x 6 h/d) but not short-access (ShA; 14 x 2 h/d) self-administration showed robust shock-induced cocaine seeking. This was associated with a heightened shock-induced prelimbic cortex Fos response and activation of cholera toxin b retro-labeled VTA neurons that project to the prelimbic cortex. Chemogenetic inhibition of this pathway using a dual virus intersectional hM4Di DREADD (designer receptor exclusively activated by designer drug) based approach prevented shock-induced cocaine seeking. Both shock-induced reinstatement and the prelimbic cortex Fos response were prevented by bilateral intra-VTA injections of the CRF receptor 1 (CRFR1) antagonist, antalarmin. Moreover, pharmacological disconnection of the CRF-regulated dopaminergic projection to the prelimbic cortex by injection of antalarmin into the VTA in one hemisphere and the D1 receptor antagonist, SCH23390, into the prelimbic cortex of the contralateral hemisphere prevented shock-induced cocaine seeking. Finally, LgA, but not ShA, cocaine self-administration resulted in increased VTA CRFR1 mRNA levels as measured using in situ hybridization. Altogether, these findings suggest that excessive cocaine use may establish susceptibility to stress-induced relapse by recruiting CRF regulation of a stressor-responsive mesocortical dopaminergic pathway.

SIGNIFICANCE STATEMENT Understanding the neural pathways and mechanisms through which stress triggers relapse to cocaine use is critical for the development of more effective treatment approaches. Prior work has demonstrated a critical role for the neuropeptide corticotropin releasing factor (CRF) in stress-induced cocaine seeking. Here we provide evidence that stress-induced reinstatement in a rat model of relapse is mediated by a CRF-regulated dopaminergic projection from the ventral tegmental area (VTA) that activates dopamine D1 receptors in the prelimbic cortex. Moreover, we report that this pathway may be recruited as a result of daily cocaine self-administration under conditions of extended drug access/heightened drug intake, likely as a result of increased CRFR1 expression in the VTA, thereby promoting susceptibility to stress-induced cocaine seeking.

in Journal of Neuroscience current issue on December 12, 2018 05:30 PM.
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Asymmetric and Distant Effects of a Unilateral Lesion of the Primary Motor Cortex on the Bilateral Supplementary Motor Areas in Adult Macaque Monkeys

A restricted lesion of the hand area in the primary motor cortex (M1) leads to a deficit of contralesional manual dexterity, followed by an incomplete functional recovery, accompanied by plastic changes in M1 itself and in other cortical areas on both hemispheres. Using the marker SMI-32 specific to pyramidal neurons in cortical layers III and V, we investigated the impact of a focal unilateral M1 lesion (hand representation) on the rostral part (F6) and caudal part (F3) of the supplementary motor area (SMA) in both hemispheres in nine adult macaque monkeys compared with four intact control monkeys. The M1 lesion induced a consistent interhemispheric asymmetry in density of SMI-32-positive neurons in F3 layer V (statistically significant in 8 of 9 lesioned monkeys), highly correlated with the lesion volume and with the duration of functional recovery, but not with the extent of functional recovery itself. Such interhemispheric asymmetry was neither present in the intact monkeys, as expected, nor in F6 in all monkeys. In addition, the M1 lesion also impacted on the basal dendritic arborization of F3 layer V neurons. Neuronal density was clearly less affected by the M1 lesion in F3 layer III compared with layer V. We interpret the remote effect of M1 lesion onto the density of SMI-32-positive neurons and dendritic arborization in the SMAs bilaterally as the consequence of multiple factors, such as changes of connectivity, diaschisis and various mechanisms involved in cortical plasticity underlying the functional recovery from the M1 lesion.

SIGNIFICANCE STATEMENT The motor system of macaque monkeys, in addition to be similarly organized as in humans, is a good candidate to study the impact of a focal lesion of the main contributor to voluntary movements, the primary motor cortex (M1), on non-primary motor cortical areas also involved in manual dexterity, both at behavioral and structural levels. Our results show that a unilateral permanent lesion of M1 hand area in nine monkeys affects the interhemispheric balance of the number of SMI-32-positive pyramidal neurons in the cortical layer V of the supplementary motor area, in a way strongly correlated to the lesion volume and duration of the incomplete functional recovery.

in Journal of Neuroscience current issue on December 12, 2018 05:30 PM.
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CK1{alpha} Collaborates with DOUBLETIME to Regulate PERIOD Function in the Drosophila Circadian Clock

The animal circadian timing system interprets environmental time cues and internal metabolic status to orchestrate circadian rhythms of physiology, allowing animals to perform necessary tasks in a time-of-day-dependent manner. Normal progression of circadian rhythms is dependent on the daily cycling of core transcriptional factors that make up cell-autonomous molecular oscillators. In Drosophila, PERIOD (PER), TIMELESS (TIM), CLOCK (CLK), and CYCLE (CYC) are core clock proteins that function in a transcriptional–translational feedback mechanism to regulate the circadian transcriptome. Posttranslational modifications of core clock proteins provide precise temporal control over when they are active as regulators of clock-controlled genes. In particular, phosphorylation is a key regulatory mechanism that dictates the subcellular localization, stability, and transcriptional activity of clock proteins. Previously, casein kinase 1α (CK1α) has been identified as a kinase that phosphorylates mammalian PER1 and modulates its stability, but the mechanisms by which it modulates PER protein stability is still unclear. Using Drosophila as a model, we show that CK1α has an overall function of speeding up PER metabolism and is required to maintain the 24 h period of circadian rhythms. Our results indicate that CK1α collaborates with the key clock kinase DOUBLETIME (DBT) in both the cytoplasm and the nucleus to regulate the timing of PER-dependent repression of the circadian transcriptome. Specifically, we observe that CK1α promotes PER nuclear localization by antagonizing the activity of DBT to inhibit PER nuclear translocation. Furthermore, CK1α enhances DBT-dependent PER phosphorylation and degradation once PER moves into the nucleus.

SIGNIFICANCE STATEMENT Circadian clocks are endogenous timers that integrate environmental signals to impose temporal control over organismal physiology over the 24 h day/night cycle. To maintain the 24 h period length of circadian clocks and to ensure that circadian rhythms are in synchrony with the external environment, key proteins that make up the molecular oscillator are extensively regulated by phosphorylation to ensure that they perform proper time-of-day-specific functions. Casein kinase 1α (CK1α) has previously been identified as a kinase that phosphorylates mammalian PERIOD (PER) proteins to promote their degradation, but the mechanism by which it modulates PER stability is unclear. In this study, we characterize the mechanisms by which CK1α interacts with DOUBLETIME (DBT) to achieve the overall function of speeding up PER metabolism and to ensure proper time-keeping.

in Journal of Neuroscience current issue on December 12, 2018 05:30 PM.
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Functional MRI in Macaque Monkeys during Task Switching

Nonhuman primates have proven to be a valuable animal model for exploring neuronal mechanisms of cognitive control. One important aspect of executive control is the ability to switch from one task to another, and task-switching paradigms have often been used in human volunteers to uncover the underlying neuronal processes. To date, however, no study has investigated task-switching paradigms in nonhuman primates during functional magnetic resonance imaging (fMRI). We trained two rhesus macaques to switch between arm movement, eye movement, and passive fixation tasks during fMRI. Similar to results obtained in human volunteers, task switching elicits increased fMRI activations in prefrontal cortex, anterior cingulate cortex, orbitofrontal cortex, and caudate nucleus. Our results indicate that the macaque monkey is a reliable model with which to investigate higher-order cognitive functioning such as task switching. As such, these results can pave the way for a detailed investigation of the neural basis of complex human behavior.

SIGNIFICANCE STATEMENT Task switching is an important aspect of cognitive control, and task-switching paradigms have often been used to investigate higher-order executive functioning in human volunteers. We used a task-switching paradigm in the nonhuman primate during fMRI and found increased activation mainly in prefrontal areas (46, 45, frontal eye field, and anterior cingulate), in orbitofrontal area 12, and in the caudate nucleus. These data fit surprisingly well with previous human imaging data, proving that the monkey is an excellent model to study task switching with high spatiotemporal resolution tools that are currently not applicable in humans. As such, our results pave the way for a detailed interrogation of regions performing similar executive functions in humans and monkeys.

in Journal of Neuroscience current issue on December 12, 2018 05:30 PM.
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Convergent Inputs from the Hippocampus and Thalamus to the Nucleus Accumbens Regulate Dopamine Neuron Activity

Aberrant hippocampal activity is observed in individuals with schizophrenia and is thought to underlie the augmented dopamine system function associated with psychosis. The pathway by which the ventral hippocampus (vHipp) regulates dopamine neuron activity has been demonstrated previously and involves a glutamatergic projection to the nucleus accumbens (NAc). Recent postmortem studies have confirmed glutamatergic abnormalities in the NAc of individuals with schizophrenia. Specifically, an increase in vesicular glutamate transporter 2 (vGlut2) expression was reported. Although projections from the hippocampus do express vGlut2, inputs from the thalamus are more likely to account for this alteration; however, the role of thalamic inputs to the NAc in the regulation of dopamine neuron activity has not been elucidated. Here, using male Sprague Dawley rats, we demonstrate that a subset of NAc medium spiny neurons receive convergent inputs from the vHipp and paraventricular nucleus of the thalamus (PVT), with both regions working synergistically to regulate dopamine neuron activity. Activation of either the vHipp or PVT increases the number of spontaneously active dopamine neurons in the ventral tegmental area. Moreover, this regulation requires simultaneous activity in both regions because PVT inactivation can reverse vHipp-induced increases in dopamine neuron population activity and vHipp inactivation can reverse PVT-induced increases. This is relevant to schizophrenia because inactivation of either the vHipp or PVT is sufficient to reverse aberrant dopamine system function in two distinct rodent models. These data suggest that thalamic abnormalities may contribute to the aberrant dopamine system function observed in schizophrenia and that the PVT represents a novel site of intervention for psychosis.

SIGNIFICANCE STATEMENT Current treatments for schizophrenia are far from adequate and a more complete understanding of the pathophysiology underlying this disease is warranted if we are to discover novel therapeutic targets. We have previously demonstrated that the aberrant dopamine system function observed in individuals with schizophrenia and rodent models is driven by increases in hippocampal activity. We now demonstrate that thalamic (paraventricular nucleus, PVT) and ventral hippocampal afferents converge in the nucleus accumbens to regulate dopamine system function. Such information provides a potential site for therapeutic intervention for schizophrenia. Indeed, inactivation of the PVT can effectively reverse aberrant dopamine system function in two distinct rodent models displaying circuit level alterations and corresponding behavioral deficits relevant to schizophrenia.

in Journal of Neuroscience current issue on December 12, 2018 05:30 PM.
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Cellular Prion Protein Mediates the Disruption of Hippocampal Synaptic Plasticity by Soluble Tau In Vivo

Intracellular neurofibrillary tangles (NFTs) composed of tau protein are a neuropathological hallmark of several neurodegenerative diseases, the most common of which is Alzheimer's disease (AD). For some time NFTs were considered the primary cause of synaptic dysfunction and neuronal death, however, more recent evidence suggests that soluble aggregates of tau are key drivers of disease. Here we investigated the effect of different tau species on synaptic plasticity in the male rat hippocampus in vivo. Intracerebroventricular injection of soluble aggregates formed from either wild-type or P301S human recombinant tau potently inhibited hippocampal long-term potentiation (LTP) at CA3-to-CA1 synapses. In contrast, tau monomers and fibrils appeared inactive. Neither baseline synaptic transmission, paired-pulse facilitation nor burst response during high-frequency conditioning stimulation was affected by the soluble tau aggregates. Similarly, certain AD brain soluble extracts inhibited LTP in a tau-dependent manner that was abrogated by either immunodepletion with, or coinjection of, a mid-region anti-tau monoclonal antibody (mAb), Tau5. Importantly, this tau-mediated block of LTP was prevented by administration of mAbs selective for the prion protein (PrP). Specifically, mAbs to both the mid-region (6D11) and N-terminus (MI-0131) of PrP prevented inhibition of LTP by both recombinant and brain-derived tau. These findings indicate that PrP is a mediator of tau-induced synaptic dysfunction.

SIGNIFICANCE STATEMENT Here we report that certain soluble forms of tau selectively disrupt synaptic plasticity in the live rat hippocampus. Further, we show that monoclonal antibodies to cellular prion protein abrogate the impairment of long-term potentiation caused both by recombinant and Alzheimer's disease brain-derived soluble tau. These findings support a critical role for cellular prion protein in the deleterious synaptic actions of extracellular soluble tau in tauopathies, including Alzheimer's disease. Thus, approaches targeting cellular prion protein, or downstream pathways, might provide an effective strategy for developing therapeutics.

in Journal of Neuroscience current issue on December 12, 2018 05:30 PM.
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Expectation Suppression Dampens Sensory Representations of Predicted Stimuli

in Journal of Neuroscience current issue on December 12, 2018 05:30 PM.
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Characterizing the Impact of Distracting Input on Visual Working Memory Representations

in Journal of Neuroscience current issue on December 12, 2018 05:30 PM.
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Neuroethics Guiding Principles for the NIH BRAIN Initiative

in Journal of Neuroscience current issue on December 12, 2018 05:30 PM.
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Neuroethics for the National Institutes of Health BRAIN Initiative

in Journal of Neuroscience current issue on December 12, 2018 05:30 PM.
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Newly Identified Electrically Coupled Neurons Support Development of the Drosophila Giant Fiber Model Circuit
Abstract
The Drosophila giant fiber (GF) escape circuit is an extensively studied model for neuron connectivity and function. Researchers have long taken advantage of the simple linear neuronal pathway, which begins at peripheral sensory modalities, travels through the central GF interneuron (GFI) to motor neurons, and terminates on wing/leg muscles. This circuit is more complex than it seems, however, as there exists a complex web of coupled neurons connected to the GFI that widely innervates the thoracic ganglion. Here, we define four new neuron clusters dye coupled to the central GFI, which we name GF coupled (GFC) 1–4. We identify new transgenic Gal4 drivers that express specifically in these neurons, and map both neuronal architecture and synaptic polarity. GFC1–4 share a central site of GFI connectivity, the inframedial bridge, where the neurons each form electrical synapses. Targeted apoptotic ablation of GFC1 reveals a key role for the proper development of the GF circuit, including the maintenance of GFI connectivity with upstream and downstream synaptic partners. GFC1 ablation frequently results in the loss of one GFI, which is always compensated for by contralateral innervation from a branch of the persisting GFI axon. Overall, this work reveals extensively coupled interconnectivity within the GF circuit, and the requirement of coupled neurons for circuit development. Identification of this large population of electrically coupled neurons in this classic model, and the ability to genetically manipulate these electrically synapsed neurons, expands the GF system capabilities for the nuanced, sophisticated circuit dissection necessary for deeper investigations into brain formation.

in eNeuro current issue on December 12, 2018 05:30 PM.
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Asymmetrical Relationship between Prediction and Control during Visuomotor Adaptation

Current theories suggest that the ability to control the body and to predict its associated sensory consequences is key for skilled motor behavior. It is also suggested that these abilities need to be updated when the mapping between motor commands and sensory consequences is altered. Here we challenge this view by investigating the transfer of adaptation to rotated visual feedback between one task in which human participants had to control a cursor with their hand in order to track a moving target, and another in which they had to predict with their eyes the visual consequences of their hand movement on the cursor. Hand and eye tracking performances were evaluated respectively through cursor–target and eye–cursor distance. Results reveal a striking dissociation: although prior adaptation of hand tracking greatly facilitates eye tracking, the adaptation of eye tracking does not transfer to hand tracking. We conclude that although the update of control is associated with the update of prediction, prediction can be updated independently of control. To account for this pattern of results, we propose that task demands mediate the update of prediction and control. Although a joint update of prediction and control seemed mandatory for success in our hand tracking task, the update of control was only facultative for success in our eye tracking task. More generally, those results promote the view that prediction and control are mediated by separate neural processes and suggest that people can learn to predict movement consequences without necessarily promoting their ability to control these movements.

in eNeuro current issue on December 12, 2018 05:30 PM.
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Biological Sex, Estradiol and Striatal Medium Spiny Neuron Physiology: A Mini-Review
Amanda A. Krentzel, John Meitzen
in Frontiers in Cellular Neuroscience | New and Recent Articles on December 12, 2018 06:00 AM.
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Contribution of Thyrotropin-Releasing Hormone to Cerebellar Long-Term Depression and Motor Learning
Masashi Watanave, Yasunori Matsuzaki, Yasuyo Nakajima, Atsushi Ozawa, Masanobu Yamada, Hirokazu Hirai
in Frontiers in Cellular Neuroscience | New and Recent Articles on December 12, 2018 06:00 AM.
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Lysophosphatidic Acid and Ion Channels as Molecular Mediators of Pain
Rebeca Juárez-Contreras, Tamara Rosenbaum, Sara L. Morales-Lázaro
in Frontiers in Molecular Neuroscience | New and Recent Articles on December 12, 2018 06:00 AM.
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Hyperforin Potentiates Antidepressant-Like Activity of Lanicemine in Mice
Bartłomiej Pochwat, Bernadeta Szewczyk, Katarzyna Kotarska, Anna Rafało-Ulińska, Marcin Siwiec, Joanna E. Sowa, Krzysztof Tokarski, Agata Siwek, Alexandre Bouron, Kristina Friedland, Gabriel Nowak
in Frontiers in Molecular Neuroscience | New and Recent Articles on December 12, 2018 06:00 AM.
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microRNAs Sculpt Neuronal Communication in a Tight Balance That Is Lost in Neurological Disease
Kristen T. Thomas, Christina Gross, Gary J. Bassell
in Frontiers in Molecular Neuroscience | New and Recent Articles on December 12, 2018 06:00 AM.
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Multi-Granularity Whole-Brain Segmentation Based Functional Network Analysis Using Resting-State fMRI
Yujing Gong, Huijun Wu, Jingyuan Li, Nizhuan Wang, Hanjun Liu, Xiaoying Tang
in Frontiers in Neuroscience | Brain Imaging Methods section | New and Recent Articles on December 12, 2018 06:00 AM.
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BindsNET: A Machine Learning-Oriented Spiking Neural Networks Library in Python
Hananel Hazan, Daniel J. Saunders, Hassaan Khan, Devdhar Patel, Darpan T. Sanghavi, Hava T. Siegelmann, Robert Kozma
in Frontiers in Neuroinformatics | New and Recent Articles on December 12, 2018 06:00 AM.
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Biocompatibility of a Magnetic Tunnel Junction Sensor Array for the Detection of Neuronal Signals in Culture
Daniela Moretti, Mattia Lorenzo DiFrancesco, Parikshit Pratim Sharma, Silvia Dante, Edoardo Albisetti, Marco Monticelli, Riccardo Bertacco, Daniela Petti, Pietro Baldelli, Fabio Benfenati
in Frontiers in Neuroscience | Neural Technology section | New and Recent Articles on December 12, 2018 06:00 AM.
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Structural organization of a major neuronal G protein regulator, the RGS7-Gβ5-R7BP complex
Signaling by the G protein Coupled Receptors (GPCRs) plays fundamental role in a vast number of essential physiological functions. Precise control of GPCR signaling requires action of Regulators of G protein Signaling (RGS) proteins that deactivate heterotrimeric G proteins. RGS proteins are elaborately regulated and comprise multiple domains and subunits, yet structural organization of these assemblies is poorly understood. Here we report a crystal structure and dynamics analyses of the multisubunit complex of RGS7, a major regulator of neuronal signaling with key roles in controlling a number of drug target GPCRs and links to neuropsychiatric disease, metabolism, and cancer. The crystal structure in combination with molecular dynamics and mass spectrometry analyses reveals unique organizational features of the complex and long-range conformational changes imposed by its constituent subunits during allosteric modulation. Notably, several intermolecular interfaces in the complex work in synergy to provide coordinated modulation of this key GPCR regulator.
in eLife: latest articles on December 12, 2018 12:00 AM.
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Muscle specific stress fibers give rise to sarcomeres in cardiomyocytes
The sarcomere is the contractile unit within cardiomyocytes driving heart muscle contraction. We sought to test the mechanisms regulating actin and myosin filament assembly during sarcomere formation. Therefore, we developed an assay using human cardiomyocytes to monitor sarcomere assembly. We report a population of muscle stress fibers, similar to actin arcs in non-muscle cells, which are essential sarcomere precursors. We show sarcomeric actin filaments arise directly from muscle stress fibers. This requires formins (e.g., FHOD3), non-muscle myosin IIA and non-muscle myosin IIB. Furthermore, we show short cardiac myosin II filaments grow to form ~1.5 µm long filaments that then 'stitch' together to form the stack of filaments at the core of the sarcomere (i.e., the A-band). A-band assembly is dependent on the proper organization of actin filaments and, as such, is also dependent on FHOD3 and myosin IIB. We use this experimental paradigm to present evidence for a unifying model of sarcomere assembly.
in eLife: latest articles on December 12, 2018 12:00 AM.
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Munc18-1 catalyzes neuronal SNARE assembly by templating SNARE association
Sec1/Munc18-family (SM) proteins are required for SNARE-mediated membrane fusion, but their mechanism(s) of action remain controversial. Using single-molecule force spectroscopy, we found that the SM protein Munc18-1 catalyzes step-wise zippering of three synaptic SNAREs (syntaxin, VAMP2, and SNAP-25) into a four-helix bundle. Catalysis requires formation of an intermediate template complex in which Munc18-1 juxtaposes the N-terminal regions of the SNARE motifs of syntaxin and VAMP2, while keeping their C-terminal regions separated. SNAP-25 binds the templated SNAREs to induce full SNARE zippering. Munc18-1 mutations modulate the stability of the template complex in a manner consistent with their effects on membrane fusion, indicating that chaperoned SNARE assembly is essential for exocytosis. Two other SM proteins, Munc18-3 and Vps33, similarly chaperone SNARE assembly via a template complex, suggesting that SM protein mechanism is conserved.
in eLife: latest articles on December 12, 2018 12:00 AM.
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The sterol-responsive RNF145 E3 ubiquitin ligase mediates the degradation of HMG-CoA reductase together with gp78 and Hrd1
Mammalian HMG-CoA reductase (HMGCR), the rate-limiting enzyme of the cholesterol biosynthetic pathway and the therapeutic target of statins, is post-transcriptionally regulated by sterol-accelerated degradation. Under cholesterol-replete conditions, HMGCR is ubiquitinated and degraded, but the identity of the E3 ubiquitin ligase(s) responsible for mammalian HMGCR turnover remains controversial. Using systematic, unbiased CRISPR/Cas9 genome-wide screens with a sterol-sensitive endogenous HMGCR reporter, we comprehensively map the E3 ligase landscape required for sterol-accelerated HMGCR degradation. We find that RNF145 and gp78 independently co-ordinate HMGCR ubiquitination and degradation. RNF145, a sterol-responsive ER-resident E3 ligase, is unstable but accumulates following sterol depletion. Sterol addition triggers RNF145 recruitment to HMGCR via Insigs, promoting HMGCR ubiquitination and proteasome-mediated degradation. In the absence of both RNF145 and gp78, Hrd1, a third UBE2G2-dependent E3 ligase, partially regulates HMGCR activity. Our findings reveal a critical role for the sterol-responsive RNF145 in HMGCR regulation and elucidate the complexity of sterol-accelerated HMGCR degradation.
in eLife: latest articles on December 12, 2018 12:00 AM.
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Role of the pre-initiation complex in Mediator recruitment and dynamics
The Mediator complex stimulates the cooperative assembly of a pre-initiation complex (PIC) and recruitment of RNA Polymerase II (Pol II) for gene activation. The core Mediator complex is organized into head, middle, and tail modules, and in budding yeast (Saccharomyces cerevisiae), Mediator recruitment has generally been ascribed to sequence-specific activators engaging the tail module triad of Med2-Med3-Med15 at upstream activating sequences (UASs). We show that yeast lacking Med2-Med3-Med15 are viable and that Mediator and PolII are recruited to promoters genome-wide in these cells, albeit at reduced levels. To test whether Mediator might alternatively be recruited via interactions with the PIC, we examined Mediator association genome-wide after depleting PIC components. We found that depletion of Taf1, Rpb3, and TBP profoundly affected Mediator association at active gene promoters, with TBP being critical for transit of Mediator from UAS to promoter, while Pol II and Taf1 stabilize Mediator association at proximal promoters.
in eLife: latest articles on December 12, 2018 12:00 AM.
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Reactive oxygen species regulate activity-dependent neuronal plasticity in Drosophila
Reactive oxygen species (ROS) have been extensively studied as damaging agents associated with ageing and neurodegenerative conditions. Their role in the nervous system under non-pathological conditions has remained poorly understood. Working with the Drosophila larval locomotor network, we show that in neurons ROS act as obligate signals required for neuronal activity-dependent structural plasticity, of both pre- and postsynaptic terminals. ROS signaling is also necessary for maintaining evoked synaptic transmission at the neuromuscular junction, and for activity-regulated homeostatic adjustment of motor network output, as measured by larval crawling behavior. We identified the highly conserved Parkinson's disease-linked protein DJ-1ß as a redox sensor in neurons where it regulates structural plasticity, in part via modulation of the PTEN-PI3Kinase pathway. This study provides a new conceptual framework of neuronal ROS as second messengers required for neuronal plasticity and for network tuning, whose dysregulation in the ageing brain and under neurodegenerative conditions may contribute to synaptic dysfunction.
in eLife: latest articles on December 12, 2018 12:00 AM.
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Characterization of the Inner and Outer Fiber Layers in the Developing Cerebral Cortex of Gyrencephalic Ferrets

Abstract
Changes in the cerebral cortex of mammals during evolution have been of great interest. Ferrets, monkeys, and humans have more developed cerebral cortices compared with mice. Although the features of progenitors in the developing cortices of these animals have been intensively investigated, those of the fiber layers are still largely elusive. By taking the advantage of our in utero electroporation technique for ferrets, here we systematically investigated the cellular origins and projection patterns of axonal fibers in the developing ferret cortex. We found that ferrets have 2 fiber layers in the developing cerebral cortex, as is the case in monkeys and humans. Axonal fibers in the inner fiber layer projected contralaterally and subcortically, whereas those in the outer fiber layer sent axons to neighboring cortical areas. Furthermore, we performed similar experiments using mice and found unexpected similarities between ferrets and mice. Our results shed light on the cellular origins, the projection patterns, the developmental processes, and the evolution of fiber layers in mammalian brains.
in Cerebral Cortex Advance Access on December 12, 2018 12:00 AM.
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Roles of Ventromedial Prefrontal Cortex and Anterior Cingulate in Subjective Valuation of Prospective Effort

Abstract
The perceived effort level of an action shapes everyday decisions. Despite the importance of these perceptions for decision-making, the behavioral and neural representations of the subjective cost of effort are not well understood. While a number of studies have implicated anterior cingulate cortex (ACC) in decisions about effort/reward trade-offs, none have experimentally isolated effort valuation from reward and choice difficulty, a function that is commonly ascribed to this region. We used functional magnetic resonance imaging to monitor brain activity while human participants engaged in uncertain choices for prospective physical effort. Our task was designed to examine effort-based decision-making in the absence of reward and separated from choice difficulty—allowing us to investigate the brain’s role in effort valuation, independent of these other factors. Participants exhibited subjectivity in their decision-making, displaying increased sensitivity to changes in subjective effort as objective effort levels increased. Analysis of blood-oxygenation-level dependent activity revealed that the ventromedial prefrontal cortex (vmPFC) encoded the subjective valuation of prospective effort, and ACC activity was best described by choice difficulty. These results provide insight into the processes responsible for decision-making regarding effort, partly dissociating the roles of vmPFC and ACC in prospective valuation of effort and choice difficulty.
in Cerebral Cortex Advance Access on December 12, 2018 12:00 AM.
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The Na+/H+ Exchanger Nhe1 Modulates Network Excitability via GABA Release

Abstract
Brain functions are extremely sensitive to pH changes because of the pH-dependence of proteins involved in neuronal excitability and synaptic transmission. Here, we show that the Na⁺/H⁺ exchanger Nhe1, which uses the Na⁺ gradient to extrude H⁺, is expressed at both inhibitory and excitatory presynapses. We disrupted Nhe1 specifically in mice either in Emx1-positive glutamatergic neurons or in parvalbumin-positive cells, mainly GABAergic interneurons. While Nhe1 disruption in excitatory neurons had no effect on overall network excitability, mice with disruption of Nhe1 in parvalbumin-positive neurons displayed epileptic activity. From our electrophysiological analyses in the CA1 of the hippocampus, we conclude that the disruption in parvalbumin-positive neurons impairs the release of GABA-loaded vesicles, but increases the size of GABA quanta. The latter is most likely an indirect pH-dependent effect, as Nhe1 was not expressed in purified synaptic vesicles itself. Conclusively, our data provide first evidence that Nhe1 affects network excitability via modulation of inhibitory interneurons.
in Cerebral Cortex Advance Access on December 12, 2018 12:00 AM.
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The Cerebral Cortex is Bisectionally Segregated into Two Fundamentally Different Functional Units of Gyri and Sulci

Abstract
The human cerebral cortex is highly folded into diverse gyri and sulci. Accumulating evidences suggest that gyri and sulci exhibit anatomical, morphological, and connectional differences. Inspired by these evidences, we performed a series of experiments to explore the frequency-specific differences between gyral and sulcal neural activities from resting-state and task-based functional magnetic resonance imaging (fMRI) data. Specifically, we designed a convolutional neural network (CNN) based classifier, which can differentiate gyral and sulcal fMRI signals with reasonable accuracies. Further investigations of learned CNN models imply that sulcal fMRI signals are more diverse and more high frequency than gyral signals, suggesting that gyri and sulci truly play different functional roles. These differences are significantly associated with axonal fiber wiring and cortical thickness patterns, suggesting that these differences might be deeply rooted in their structural and cellular underpinnings. Further wavelet entropy analyses demonstrated the validity of CNN-based findings. In general, our collective observations support a new concept that the cerebral cortex is bisectionally segregated into 2 functionally different units of gyri and sulci.
in Cerebral Cortex Advance Access on December 12, 2018 12:00 AM.
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SFPEL-LPI: Sequence-based feature projection ensemble learning for predicting LncRNA-protein interactions

by Wen Zhang, Xiang Yue, Guifeng Tang, Wenjian Wu, Feng Huang, Xining Zhang
LncRNA-protein interactions play important roles in post-transcriptional gene regulation, poly-adenylation, splicing and translation. Identification of lncRNA-protein interactions helps to understand lncRNA-related activities. Existing computational methods utilize multiple lncRNA features or multiple protein features to predict lncRNA-protein interactions, but features are not available for all lncRNAs or proteins; most of existing methods are not capable of predicting interacting proteins (or lncRNAs) for new lncRNAs (or proteins), which don’t have known interactions. In this paper, we propose the sequence-based feature projection ensemble learning method, “SFPEL-LPI”, to predict lncRNA-protein interactions. First, SFPEL-LPI extracts lncRNA sequence-based features and protein sequence-based features. Second, SFPEL-LPI calculates multiple lncRNA-lncRNA similarities and protein-protein similarities by using lncRNA sequences, protein sequences and known lncRNA-protein interactions. Then, SFPEL-LPI combines multiple similarities and multiple features with a feature projection ensemble learning frame. In computational experiments, SFPEL-LPI accurately predicts lncRNA-protein associations and outperforms other state-of-the-art methods. More importantly, SFPEL-LPI can be applied to new lncRNAs (or proteins). The case studies demonstrate that our method can find out novel lncRNA-protein interactions, which are confirmed by literature. Finally, we construct a user-friendly web server, available at http://www.bioinfotech.cn/SFPEL-LPI/.
in PLOS Computational Biology: New Articles on December 11, 2018 10:00 PM.
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PremPDI estimates and interprets the effects of missense mutations on protein-DNA interactions

by Ning Zhang, Yuting Chen, Feiyang Zhao, Qing Yang, Franco L. Simonetti, Minghui Li
Protein-DNA interactions play important roles in regulations of many vital cellular processes, including transcription, translation, DNA replication and recombination. Sequence variants occurring in these DNA binding proteins that alter protein-DNA interactions may cause significant perturbations or complete abolishment of function, potentially leading to diseases. Developing a mechanistic understanding of impacts of variants on protein-DNA interactions becomes a persistent need. To address this need we introduce a new computational method PremPDI that predicts the effect of single missense mutation in the protein on the protein-DNA interaction and calculates the quantitative binding affinity change. The PremPDI method is based on molecular mechanics force fields and fast side-chain optimization algorithms with parameters optimized on experimental sets of 219 mutations from 49 protein-DNA complexes. PremPDI yields a very good agreement between predicted and experimental values with Pearson correlation coefficient of 0.71 and root-mean-square error of 0.86 kcal mol^-1. The PremPDI server could map mutations on a structural protein-DNA complex, calculate the associated changes in binding affinity, determine the deleterious effect of a mutation, and produce a mutant structural model for download. PremPDI can be applied to many tasks, such as determination of potential damaging mutations in cancer and other diseases. PremPDI is available at http://lilab.jysw.suda.edu.cn/research/PremPDI/.
in PLOS Computational Biology: New Articles on December 11, 2018 10:00 PM.
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Retraction for Baradaran-Heravi et al., Gentamicin B1 is a minor gentamicin component with major nonsense mutation suppression activity [Retractions]
GENETICS Retraction for “Gentamicin B1 is a minor gentamicin component with major nonsense mutation suppression activity,” by Alireza Baradaran-Heravi, Jürgen Niesser, Aruna D. Balgi, Kunho Choi, Carla Zimmerman, Andrew P. South, Hilary J. Anderson, Natalie C. Strynadka, Marcel B. Bally, and Michel Roberge, which was first published March 13, 2017;...
in Proceedings of the National Academy of Sciences Recent Issues on December 11, 2018 06:16 PM.
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Correction for Yoon et al., Control of movement vigor and decision making during foraging [Corrections]
NEUROSCIENCE, PSYCHOLOGICAL AND COGNITIVE SCIENCES Correction for “Control of movement vigor and decision making during foraging,” by Tehrim Yoon, Robert B. Geary, Alaa A. Ahmed, and Reza Shadmehr, which was first published October 15, 2018; 10.1073/pnas.1812979115 (Proc Natl Acad Sci USA 115:E10476–E10485). The authors note that, due to a printer’s...
in Proceedings of the National Academy of Sciences Recent Issues on December 11, 2018 06:16 PM.
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Metabolic network-based stratification of hepatocellular carcinoma reveals three distinct tumor subtypes [Systems Biology]
Hepatocellular carcinoma (HCC) is one of the most frequent forms of liver cancer, and effective treatment methods are limited due to tumor heterogeneity. There is a great need for comprehensive approaches to stratify HCC patients, gain biological insights into subtypes, and ultimately identify effective therapeutic targets. We stratified HCC patients...
in Proceedings of the National Academy of Sciences Recent Issues on December 11, 2018 06:16 PM.
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Hinge region of Arabidopsis phyA plays an important role in regulating phyA function [Plant Biology]
Phytochrome A (phyA) is the only plant photoreceptor that perceives far-red light and then mediates various responses to this signal. Phosphorylation and dephosphorylation of oat phyA have been extensively studied, and it was shown that phosphorylation of a serine residue in the hinge region of oat phyA could regulate the...
in Proceedings of the National Academy of Sciences Recent Issues on December 11, 2018 06:16 PM.
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PYL8 mediates ABA perception in the root through non-cell-autonomous and ligand-stabilization-based mechanisms [Plant Biology]
The phytohormone abscisic acid (ABA) plays a key role regulating root growth, root system architecture, and root adaptive responses, such as hydrotropism. The molecular and cellular mechanisms that regulate the action of core ABA signaling components in roots are not fully understood. ABA is perceived through receptors from the PYR/PYL/RCAR...
in Proceedings of the National Academy of Sciences Recent Issues on December 11, 2018 06:16 PM.
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Role of human Hv1 channels in sperm capacitation and white blood cell respiratory burst established by a designed peptide inhibitor [Physiology]
Using a de novo peptide inhibitor, Corza6 (C6), we demonstrate that the human voltage-gated proton channel (hHv1) is the main pathway for H+ efflux that allows capacitation in sperm and permits sustained reactive oxygen species (ROS) production in white blood cells (WBCs). C6 was identified by a phage-display strategy whereby...
in Proceedings of the National Academy of Sciences Recent Issues on December 11, 2018 06:16 PM.
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TRPV1 pore turret dictates distinct DkTx and capsaicin gating [Pharmacology]
Many neurotoxins inflict pain by targeting receptors expressed on nociceptors, such as the polymodal cationic channel TRPV1. The tarantula double-knot toxin (DkTx) is a peptide with an atypical bivalent structure, providing it with the unique capability to lock TRPV1 in its open state and evoke an irreversible channel activation. Here,...
in Proceedings of the National Academy of Sciences Recent Issues on December 11, 2018 06:16 PM.
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Interplay of the Norrin and Wnt7a/Wnt7b signaling systems in blood-brain barrier and blood-retina barrier development and maintenance [Neuroscience]
β-Catenin signaling controls the development and maintenance of the blood–brain barrier (BBB) and the blood–retina barrier (BRB), but the division of labor and degree of redundancy between the two principal ligand–receptor systems—the Norrin and Wnt7a/Wnt7b systems—are incompletely defined. Here, we present a loss-of-function genetic analysis of postnatal BBB and BRB...
in Proceedings of the National Academy of Sciences Recent Issues on December 11, 2018 06:16 PM.
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Photoreceptive retinal ganglion cells control the information rate of the optic nerve [Neuroscience]
Information transfer in the brain relies upon energetically expensive spiking activity of neurons. Rates of information flow should therefore be carefully optimized, but mechanisms to control this parameter are poorly understood. We address this deficit in the visual system, where ambient light (irradiance) is predictive of the amount of information...
in Proceedings of the National Academy of Sciences Recent Issues on December 11, 2018 06:16 PM.
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The adult oligodendrocyte can participate in remyelination [Neuroscience]
Endogenous remyelination of the CNS can be robust and restore function, yet in multiple sclerosis it becomes less complete with time. Promoting remyelination is a major therapeutic goal, both to restore function and to protect axons from degeneration. Remyelination is thought to depend on oligodendrocyte progenitor cells, giving rise to...
in Proceedings of the National Academy of Sciences Recent Issues on December 11, 2018 06:16 PM.
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Emergent elasticity in the neural code for space [Neuroscience]
Upon encountering a novel environment, an animal must construct a consistent environmental map, as well as an internal estimate of its position within that map, by combining information from two distinct sources: self-motion cues and sensory landmark cues. How do known aspects of neural circuit dynamics and synaptic plasticity conspire...
in Proceedings of the National Academy of Sciences Recent Issues on December 11, 2018 06:16 PM.
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Integrative approach using Yersinia pestis genomes to revisit the historical landscape of plague during the Medieval Period [Microbiology]
Over the last few years, genomic studies on Yersinia pestis, the causative agent of all known plague epidemics, have considerably increased in numbers, spanning a period of about 5,000 y. Nonetheless, questions concerning historical reservoirs and routes of transmission remain open. Here, we present and describe five genomes from the...
in Proceedings of the National Academy of Sciences Recent Issues on December 11, 2018 06:16 PM.
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DksA-DnaJ redox interactions provide a signal for the activation of bacterial RNA polymerase [Microbiology]
RNA polymerase is the only known protein partner of the transcriptional regulator DksA. Herein, we demonstrate that the chaperone DnaJ establishes direct, redox-based interactions with oxidized DksA. Cysteine residues in the zinc finger of DksA become oxidized in Salmonella exposed to low concentrations of hydrogen peroxide (H2O2). The resulting disulfide...
in Proceedings of the National Academy of Sciences Recent Issues on December 11, 2018 06:16 PM.
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Staphylococcus aureus coagulases are exploitable yet stable public goods in clinically relevant conditions [Microbiology]
Coagulation is an innate defense mechanism intended to limit blood loss and trap invading pathogens during infection. However, Staphylococcus aureus has the ability to hijack the coagulation cascade and generate clots via secretion of coagulases. Although many S. aureus have this characteristic, some do not. The population dynamics regarding this...
in Proceedings of the National Academy of Sciences Recent Issues on December 11, 2018 06:16 PM.
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Comparative genomics reveals the molecular determinants of rapid growth of the cyanobacterium Synechococcus elongatus UTEX 2973 [Microbiology]
Cyanobacteria are emerging as attractive organisms for sustainable bioproduction. We previously described Synechococcus elongatus UTEX 2973 as the fastest growing cyanobacterium known. Synechococcus 2973 exhibits high light tolerance and an increased photosynthetic rate and produces biomass at three times the rate of its close relative, the model strain Synechococcus elongatus...
in Proceedings of the National Academy of Sciences Recent Issues on December 11, 2018 06:16 PM.
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Structure and architecture of immature and mature murine leukemia virus capsids [Microbiology]
Retroviruses assemble and bud from infected cells in an immature form and require proteolytic maturation for infectivity. The CA (capsid) domains of the Gag polyproteins assemble a protein lattice as a truncated sphere in the immature virion. Proteolytic cleavage of Gag induces dramatic structural rearrangements; a subset of cleaved CA...
in Proceedings of the National Academy of Sciences Recent Issues on December 11, 2018 06:16 PM.
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Citrate-based materials fuel human stem cells by metabonegenic regulation [Medical Sciences]
A comprehensive understanding of the key microenvironmental signals regulating bone regeneration is pivotal for the effective design of bioinspired orthopedic materials. Here, we identified citrate as an osteopromotive factor and revealed its metabonegenic role in mediating citrate metabolism and its downstream effects on the osteogenic differentiation of human mesenchymal stem...
in Proceedings of the National Academy of Sciences Recent Issues on December 11, 2018 06:16 PM.
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CD226 regulates natural killer cell antitumor responses via phosphorylation-mediated inactivation of transcription factor FOXO1 [Immunology and Inflammation]
Natural killer (NK) cell recognition of tumor cells is mediated through activating receptors such as CD226, with suppression of effector functions often controlled by negative regulatory transcription factors such as FOXO1. Here we show that CD226 regulation of NK cell cytotoxicity is facilitated through inactivation of FOXO1. Gene-expression analysis of...
in Proceedings of the National Academy of Sciences Recent Issues on December 11, 2018 06:16 PM.
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Molecular mechanisms of biogenesis of apoptotic exosome-like vesicles and their roles as damage-associated molecular patterns [Immunology and Inflammation]
Recent research has led to contradictory notions regarding the conventional theory that apoptotic cell death can evoke inflammatory or immunogenic responses orchestrated by released damage-associated patterns (DAMPs). By inducing IL-1β from bone marrow-derived macrophages in an effort to determine the inflammatory mediators released from apoptotic cells, we found that exosomal...
in Proceedings of the National Academy of Sciences Recent Issues on December 11, 2018 06:16 PM.
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Transcriptional landscape of B cell precursor acute lymphoblastic leukemia based on an international study of 1,223 cases [Genetics]
Most B cell precursor acute lymphoblastic leukemia (BCP ALL) can be classified into known major genetic subtypes, while a substantial proportion of BCP ALL remains poorly characterized in relation to its underlying genomic abnormalities. We therefore initiated a large-scale international study to reanalyze and delineate the transcriptome landscape of 1,223...
in Proceedings of the National Academy of Sciences Recent Issues on December 11, 2018 06:16 PM.
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MicroRNA-22 Controls Aberrant Neurogenesis and Changes in Neuronal Morphology After Status Epilepticus
Edward H. Beamer, Jeronimo Jurado-Arjona, Eva M. Jimenez-Mateos, James Morgan, Cristina R. Reschke, Aidan Kenny, Gioacchino de Leo, Luis A. Olivos-Oré, Marina Arribas-Blázquez, Stephen F. Madden, Jesús Merchán-Rubira, Norman Delanty, Michael A. Farrell, Donncha F. O’Brien, Jesus Avila, Miguel Diaz-Hernandez, M. Teresa Miras-Portugal, Antonio R. Artalejo, Felix Hernandez, David C. Henshall, Tobias Engel
in Frontiers in Molecular Neuroscience | New and Recent Articles on December 11, 2018 06:00 PM.
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Affective Network Neuroscience
Sebastian Markett, Olga A. Wudarczyk, Bharat B. Biswal, Philippe Jawinski, Christian Montag
in Frontiers in Neuroscience | Brain Imaging Methods section | New and Recent Articles on December 11, 2018 06:00 PM.
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3DMorph Automatic Analysis of Microglial Morphology in Three Dimensions from Ex Vivo and In Vivo Imaging

Microglia are dynamic immune cells of the central nervous system, and their morphology is commonly used as a readout of cellular function. However, current morphological analysis techniques rely on either tracing of cells or two-dimensional projection analysis, which are time-consuming, subject to bias, and may ignore important three-dimensional (3D) information. Therefore, we have created 3DMorph, a MATLAB-based script that analyzes microglial morphology from 3D data. The program initially requires input of threshold levels, cell size expectations, and preferred methods of skeletonization. This makes 3DMorph easily scalable and adaptable to different imaging parameters or cell types. After these settings are defined, the program is completely automatic and can batch process files without user input. Output data includes cell volume, territorial volume, branch length, number of endpoints and branch points, and average distance between cells. We show that 3DMorph is accurate compared to manual tracing, with significantly decreased user input time. Importantly, 3DMorph is capable of processing in vivo microglial morphology, as well as other 3D branching cell types, from mouse cranial windows or acute hippocampal slices. Therefore, we present a novel, user-friendly, scalable, and semiautomatic method of analyzing cell morphology in 3 dimensions. This method should improve the accuracy of cell measurements, remove user bias between conditions, increase reproducibility between experimenters and labs, and reduce user input time. We provide this open source code on GitHub so that it is free and accessible to all investigators.

in eNeuro current issue on December 11, 2018 05:32 PM.
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A Gate-and-Switch Model for Head Orientation Behaviors in Caenorhabditis elegans
Abstract
The nervous system seamlessly integrates perception and action. This ability is essential for stable representation of and appropriate responses to the external environment. How the sensorimotor integration underlying this ability occurs at the level of individual neurons is of keen interest. In Caenorhabditis elegans, RIA interneurons receive input from sensory pathways and have reciprocal connections with head motor neurons. RIA simultaneously encodes both head orientation and sensory stimuli, which may allow it to integrate these two signals to detect the spatial distribution of stimuli across head sweeps and generate directional head responses. Here, we show that blocking synaptic release from RIA disrupts head orientation behaviors in response to unilaterally presented stimuli. We found that sensory encoding in RIA is gated according to head orientation. This dependence on head orientation is independent of motor encoding in RIA, suggesting a second, posture-dependent pathway upstream of RIA. This gating mechanism may allow RIA to selectively attend to stimuli that are asymmetric across head sweeps. Attractive odor removal during head bends triggers rapid head withdrawal in the opposite direction. Unlike sensory encoding, this directional response is dependent on motor inputs to and synaptic output from RIA. Together, these results suggest that RIA is part of a sensorimotor pathway that is dynamically regulated according to head orientation at two levels: the first is a gate that filters sensory representations in RIA, and the second is a switch that routes RIA synaptic output to dorsal or ventral head motor neurons.

in eNeuro current issue on December 11, 2018 05:32 PM.
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State Anxiety Down-Regulates Empathic Responses: Electrophysiological Evidence
Pinchao Luo, Mengdi Zhuang, Jing Jie, Xiayun Wu, Xifu Zheng
in Frontiers in Human Neuroscience | New and Recent Articles on December 11, 2018 06:00 AM.
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Different Aspects of the Neural Response to Socio-Emotional Events Are Related to Instability and Inertia of Emotional Experience in Daily Life: An fMRI-ESM Study
Julian Provenzano, Jojanneke A. Bastiaansen, Philippe Verduyn, Albertine J. Oldehinkel, Philippe Fossati, Peter Kuppens
in Frontiers in Human Neuroscience | New and Recent Articles on December 11, 2018 06:00 AM.
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Modulation of Item and Source Memory by Auditory Beat Stimulation: A Pilot Study With Intracranial EEG
Marlene Derner, Leila Chaieb, Rainer Surges, Bernhard P. Staresina, Juergen Fell
in Frontiers in Human Neuroscience | New and Recent Articles on December 11, 2018 06:00 AM.
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Lower Local Dynamic Stability and Invariable Orbital Stability in the Activation of Muscle Synergies in Response to Accelerated Walking Speeds
Benio Kibushi, Shota Hagio, Toshio Moritani, Motoki Kouzaki
in Frontiers in Human Neuroscience | New and Recent Articles on December 11, 2018 06:00 AM.
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Inactivation of Cyclin-Dependent Kinase 5 in Hair Cells Causes Hearing Loss in Mice
Xiaoyan Zhai, Chengcheng Liu, Bin Zhao, Yanfei Wang, Zhigang Xu
in Frontiers in Molecular Neuroscience | New and Recent Articles on December 11, 2018 06:00 AM.
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Yeast Models of Prion-Like Proteins That Cause Amyotrophic Lateral Sclerosis Reveal Pathogenic Mechanisms
Zachary T. Monahan, Shannon N. Rhoads, Debra S. Yee, Frank P. Shewmaker
in Frontiers in Molecular Neuroscience | New and Recent Articles on December 11, 2018 06:00 AM.
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An Immune-CNS Axis Activates Remote Hippocampal Stem Cells Following Spinal Transection Injury
Sascha Dehler, Wilson Pak-Kin Lou, Liang Gao, Maxim Skabkin, Sabrina Dällenbach, Andreas Neumann, Ana Martin-Villalba
in Frontiers in Molecular Neuroscience | New and Recent Articles on December 11, 2018 06:00 AM.
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ROCK Inhibitor Y27632 Induced Morphological Shift and Enhanced Neurite Outgrowth-Promoting Property of Olfactory Ensheathing Cells via YAP-Dependent Up-Regulation of L1-CAM
Yijian Li, Shujia Huo, Yajie Fang, Ting Zou, Xianliang Gu, Qin Tao, Haiwei Xu
in Frontiers in Cellular Neuroscience | New and Recent Articles on December 11, 2018 06:00 AM.
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Seizure-Induced Potentiation of AMPA Receptor-Mediated Synaptic Transmission in the Entorhinal Cortex
Dmitry V. Amakhin, Elena B. Soboleva, Julia L. Ergina, Sergey L. Malkin, Anton V. Chizhov, Aleksey V. Zaitsev
in Frontiers in Cellular Neuroscience | New and Recent Articles on December 11, 2018 06:00 AM.
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The Role of Glial Cells and Synapse Loss in Mouse Models of Alzheimer’s Disease
Stephanie Ziegler-Waldkirch, Melanie Meyer-Luehmann
in Frontiers in Cellular Neuroscience | New and Recent Articles on December 11, 2018 06:00 AM.
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Multi-Beam Scanning Electron Microscopy for High-Throughput Imaging in Connectomics Research
Anna Lena Eberle, Dirk Zeidler
in Frontiers in Neuroanatomy | New and Recent Articles on December 11, 2018 06:00 AM.
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Jacobian Maps Reveal Under-reported Brain Regions Sensitive to Extreme Binge Ethanol Intoxication in the Rat
Qingyu Zhao, Michael Fritz, Adolf Pfefferbaum, Edith V. Sullivan, Kilian M. Pohl, Natalie M. Zahr
in Frontiers in Neuroanatomy | New and Recent Articles on December 11, 2018 06:00 AM.
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Editorial: Neuroinflammation and Cognition
Ashok Kumar
in Frontiers in Aging Neuroscience | New and Recent Articles on December 11, 2018 06:00 AM.
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Plasma Protein Biomarkers for the Prediction of CSF Amyloid and Tau and [18F]-Flutemetamol PET Scan Result
Sarah Westwood, Alison L. Baird, Abdul Hye, Nicholas J. Ashton, Alejo J. Nevado-Holgado, Sneha N. Anand, Benjamine Liu, Danielle Newby, Chantal Bazenet, Steven J. Kiddle, Malcolm Ward, Ben Newton, Keyur Desai, Cristina Tan Hehir, Michelle Zanette, Daniela Galimberti, Lucilla Parnetti, Alberto Lleó, Susan Baker, Vaibhav A. Narayan, Wiesje M. van der Flier, Philip Scheltens, Charlotte E. Teunissen, Pieter Jelle Visser, Simon Lovestone
in Frontiers in Aging Neuroscience | New and Recent Articles on December 11, 2018 06:00 AM.
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Vestibular Function and Beta-Amyloid Deposition in the Baltimore Longitudinal Study of Aging
Rebecca J. Kamil, Murat Bilgel, Dean F. Wong, Susan M. Resnick, Yuri Agrawal
in Frontiers in Aging Neuroscience | New and Recent Articles on December 11, 2018 06:00 AM.
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Perforant Path Fiber Loss Results in Mnemonic Discrimination Task Deficits in Young Rats
Sara N. Burke, Sean M. Turner, Courtney L. Desrosiers, Sarah A. Johnson, Andrew P. Maurer
in Frontiers in Systems Neuroscience | New and Recent Articles on December 11, 2018 06:00 AM.
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Mechanisms of Supralinear Calcium Integration in Dendrites of Hippocampal CA1 Fast-Spiking Cells
Olivier Camiré, Ivan Lazarevich, Tommy Gilbert, Lisa Topolnik
in Frontiers in Synaptic Neuroscience | New and Recent Articles on December 11, 2018 06:00 AM.
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Mechanisms Involved in the Neuroprotection of Electroacupuncture Therapy for Ischemic Stroke
Ying Xing, Min Zhang, Wen-Bin Li, Fang Dong, Feng Zhang
in Frontiers in Neuroscience | Neural Technology section | New and Recent Articles on December 11, 2018 06:00 AM.
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Characterization of Axon Damage, Neurological Deficits, and Histopathology in Two Experimental Models of Intracerebral Hemorrhage
Yao Liu, Gang Lu, Xian Wei Su, Tao Ding, Wen Li Wang, Yong Mei Li, Wai Sang Poon, Li Juan Ao
in Frontiers in Neuroscience | Neurodegeneration section | New and Recent Articles on December 11, 2018 06:00 AM.
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Regulation of Chromatin Structure During Neural Development
Yusuke Kishi, Yukiko Gotoh
in Frontiers in Neuroscience | Neurogenesis section | New and Recent Articles on December 11, 2018 06:00 AM.
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Initial-Dip Existence and Estimation in Relation to DPF and Data Drift
Muhammad A. Kamran, Malik M. Naeem Mannan, Myung-Yung Jeong
in Frontiers in Neuroinformatics | New and Recent Articles on December 11, 2018 06:00 AM.
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Mapping Histological Slice Sequences to the Allen Mouse Brain Atlas Without 3D Reconstruction
Jing Xiong, Jing Ren, Liqun Luo, Mark Horowitz
in Frontiers in Neuroinformatics | New and Recent Articles on December 11, 2018 06:00 AM.
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Suppression of Parkinsonian Beta Oscillations by Deep Brain Stimulation: Determination of Effective Protocols
Eli J. Müller, Peter A. Robinson
in Frontiers in Computational Neuroscience | New and Recent Articles on December 11, 2018 06:00 AM.
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Stability of spontaneous, correlated activity in mouse auditory cortex. (arXiv:1812.03796v1 [q-bio.NC])

Neural systems can be modeled as networks of functionally connected neural elements. The resulting network can be analyzed using mathematical tools from network science and graph theory to quantify the system's topological organization and to better understand its function. While the network-based approach is common in the analysis of large-scale neural systems probed by non-invasive neuroimaging, few studies have used network science to study the organization of networks reconstructed at the cellular level, and thus many very basic and fundamental questions remain unanswered. Here, we used two-photon calcium imaging to record spontaneous activity from the same set of cells in mouse auditory cortex over the course of several weeks. We reconstruct functional networks in which cells are linked to one another by edges weighted according to the correlation of their fluorescence traces. We show that the networks exhibit modular structure across multiple topological scales and that these multi-scale modules unfold as part of a hierarchy. We also show that, on average, network architecture becomes increasingly dissimilar over time, with similarity decaying monotonically with the distance (in time) between sessions. Finally, we show that a small fraction of cells maintain strongly-correlated activity over multiple days, forming a stable temporal core surrounded by a fluctuating and variable periphery. Our work provides a careful methodological blueprint for future studies of spontaneous activity measured by two-photon calcium imaging using cutting-edge computational methods and machine learning algorithms informed by explicit graphical models from network science. The methods are easily extended to additional datasets, opening the possibility of studying cellular level network organization of neural systems and how that organization is modulated by stimuli or altered in models of disease.

in q-bio.NC updates on arXiv.org on December 11, 2018 01:30 AM.
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Guided Graph Spectral Embedding: Application to the C. elegans Connectome. (arXiv:1812.03684v1 [cs.LG])

Graph spectral analysis can yield meaningful embeddings of graphs by providing insight into distributed features not directly accessible in nodal domain. Recent efforts in graph signal processing have proposed new decompositions-e.g., based on wavelets and Slepians-that can be applied to filter signals defined on the graph. In this work, we take inspiration from these constructions to define a new guided spectral embedding that combines maximizing energy concentration with minimizing modified embedded distance for a given importance weighting of the nodes. We show these optimization goals are intrinsically opposite, leading to a well-defined and stable spectral decomposition. The importance weighting allows to put the focus on particular nodes and tune the trade-off between global and local effects. Following the derivation of our new optimization criterion and its linear approximation, we exemplify the methodology on the C. elegans structural connectome. The results of our analyses confirm known observations on the nematode's neural network in terms of functionality and importance of cells. Compared to Laplacian embedding, the guided approach, focused on a certain class of cells (sensory, inter- and motoneurons), provides more biological insights, such as the distinction between somatic positions of cells, and their involvement in low or high order processing functions.

in q-bio.NC updates on arXiv.org on December 11, 2018 01:30 AM.
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Role of NMDA conductance in average firing rate shifts caused by external periodic forcing. (arXiv:1812.03609v1 [q-bio.NC])

A widely accepted view of computations in the brain relies on population coding, where the neural ensemble firing rate is modulated in a stable manner to transmit information and perform various cognitive tasks. At the same time, oscillatory neural activity is specifically modulated in frequency, coherence and power during cognitive performance. How the firing rate and oscillations interact remains a salient question. In this paper, we develop a theory for the interactions between oscillatory signals and the firing rate of neural populations based on activity of non-linear voltage-dependent NMDA synapses. Notably, we show under which conditions oscillatory inputs can control the mean firing rate without loss of stability. Using mathematical analysis and simulations of mean-field models, we demonstrate that presence of NMDA synapses on both the excitatory and the inhibitory neurons is critical for sinusoidal oscillations to significantly and stably increase the firing rate. We characterize the oscillation-induced mean firing rate shift as a function of the fast and slow synaptic weights and demonstrate the parameter region, in which the effect under investigation is mostly pronounced. Results of our work may help identify the properties of neural circuits that allow for constructive control of the firing rate codes by large-scale neural oscillations.

in q-bio.NC updates on arXiv.org on December 11, 2018 01:30 AM.
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Macroscopic phase resetting-curves determine oscillatory coherence and signal transfer in inter-coupled neural circuits. (arXiv:1812.03455v1 [q-bio.NC])

Macroscopic oscillations of different brain regions show multiple phase relationships that are persistent across time and have been implicated routing information. Various cellular level mechanisms influence the network dynamics and structure the macroscopic firing patterns. Key question is to identify the biophysical neuronal and synaptic properties that permit such motifs to arise and how the different coherence states determine the communication between the neural circuits. We analyse the emergence of phase locking within bidirectionally delayed-coupled spiking circuits showing global gamma band oscillations. We consider both the interneuronal (ING) and the pyramidal-interneuronal (PING) gamma rhythms and the inter coupling targeting the pyramidal or the inhibitory interneurons. Using a mean-field approach together with an exact reduction method, we break down each spiking network into a low dimensional nonlinear system and derive the macroscopic phase resetting-curves (mPRCs) that determine how the phase of the global oscillation responds to incoming perturbations. Depending on the type of gamma oscillation, we show that incoming excitatory inputs can either only speed up the oscillation (phase advance; type I PRC) or induce both an advance and a delay the macroscopic oscillation (phase delay; type II PRC). From there we determine the structure of macroscopic coherence states (phase locking) of two weakly synaptically-coupled networks. To do so we derive a phase equation for the coupled system which links the synaptic mechanisms to the coherence state of the system. We show that the transmission delay is a necessary condition for symmetry breaking, i.e. a non-symmetric phase lag between the macroscopic oscillations, potentially giving an explanation to the experimentally observed variety of gamma phase-locking modes.

in q-bio.NC updates on arXiv.org on December 11, 2018 01:30 AM.
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The lure of causal statements: Rampant mis-inference of causality in estimated connectivity. (arXiv:1812.03363v1 [q-bio.NC])

As neuroscientists we want to understand how causal interactions or mechanisms within the brain give rise to perception, cognition, and behavior. It is typical to estimate interaction effects from measured activity using statistical techniques such as functional connectivity, Granger Causality,or information flow, whose outcomes are often falsely treated as revealing mechanistic insight. Since these statistical techniques fit models to low-dimensional measurements from brains, they ignore the fact that brain activity is high-dimensional. Here we focus on the obvious confound of common inputs: the countless unobserved variables likely have more influence than the few observed ones. Any given observed correlation can be explained by an infinite set of causal models that take into account the unobserved variables. Therefore, correlations within massively undersampled measurements tell us little about mechanisms. We argue that these mis-inferences of causality from correlation are augmented by an implicit redefinition of words that suggest mechanisms, such as connectivity, causality, and flow.

in q-bio.NC updates on arXiv.org on December 11, 2018 01:30 AM.
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HIPPO signaling resolves embryonic cell fate conflicts during establishment of pluripotency in vivo
During mammalian development, the challenge for the embryo is to override intrinsic cellular plasticity to drive cells to distinct fates. Here, we unveil novel roles for the HIPPO signaling pathway in controlling cell positioning and expression of Sox2, the first marker of pluripotency in the mouse early embryo. We show that maternal and zygotic YAP1 and WWTR1 repress Sox2 while promoting expression of the trophectoderm gene Cdx2 in parallel. Yet, Sox2 is more sensitive than Cdx2 to Yap1/Wwtr1 dosage, leading cells to a state of conflicted cell fate when YAP1/WWTR1 activity is moderate. Remarkably, HIPPO signaling activity resolves conflicted cell fate by repositioning cells to the interior of the embryo, independent of its role in regulating Sox2 expression. Rather, HIPPO antagonizes apical localization of Par complex components PARD6B and aPKC. Thus, negative feedback between HIPPO and Par complex components ensure robust lineage segregation.
in eLife: latest articles on December 11, 2018 12:00 AM.
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Voltage-dependent dynamics of the BK channel cytosolic gating ring are coupled to the membrane-embedded voltage sensor
In human large conductance voltage- and calcium-dependent potassium (BK) channels are regulated allosterically by transmembrane voltage and intracellular Ca²⁺. Divalent cation binding sites reside within the gating ring formed by two Regulator of Conductance of Potassium (RCK) domains per subunit. Using patch-clamp fluorometry, we show that Ca²⁺ binding to the RCK1 domain triggers gating ring rearrangements that depend on transmembrane voltage. Because the gating ring is outside the electric field, this voltage sensitivity must originate from coupling to the voltage-dependent channel opening, the voltage sensor or both. Here we demonstrate that alterations of the voltage sensor, either by mutagenesis or regulation by auxiliary subunits, are paralleled by changes in the voltage dependence of the gating ring movements, whereas modifications of the relative open probability are not. These results strongly suggest that conformational changes of RCK1 domains are specifically coupled to the voltage sensor function during allosteric modulation of BK channels.
in eLife: latest articles on December 11, 2018 12:00 AM.
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Convergence of monosynaptic and polysynaptic sensory paths onto common motor outputs in a Drosophila feeding connectome
We reconstructed, from a whole CNS EM volume, the synaptic map of input and output neurons that underlie food intake behavior of Drosophila larvae. Input neurons originate from enteric, pharyngeal and external sensory organs and converge onto seven distinct sensory synaptic compartments within the CNS. Output neurons consist of feeding motor, serotonergic modulatory and neuroendocrine neurons. Monosynaptic connections from a set of sensory synaptic compartments cover the motor, modulatory and neuroendocrine targets in overlapping domains. Polysynaptic routes are superimposed on top of monosynaptic connections, resulting in divergent sensory paths that converge on common outputs. A completely different set of sensory compartments is connected to the mushroom body calyx. The mushroom body output neurons are connected to interneurons that directly target the feeding output neurons. Our results illustrate a circuit architecture in which monosynaptic and multisynaptic connections from sensory inputs traverse onto output neurons via a series of converging paths.
in eLife: latest articles on December 11, 2018 12:00 AM.
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Axoglial Adhesion by Cadm4 Regulates CNS Myelination
Elazar et al. demonstrate that myelination requires regulated adhesive interactions between oligodendrocytes and axons. They show that excessive axoglial contact results in mistargeting of oligodendrocytes to neuronal somata and their inability to form elongated myelin around axons.
in Neuron on December 11, 2018 12:00 AM.
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Engram Cell Excitability State Determines the Efficacy of Memory Retrieval
Memory exists across different time scales. Long-term memories can last a lifetime, while working memory persists for mere seconds. In between, memories that are newly formed—or recently recalled—are more vivid than latent ones. How does this happen? The act of memory recall increases the excitability of whole engram cells for about one hour. This short-term increase of engram cell excitability facilitates synaptic access to memory content in response to relevant environmental cues.
in Neuron on December 11, 2018 12:00 AM.
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Altered Slc25 family gene expression as markers of mitochondrial dysfunction in brain regions under experimental mixed anxiety/depression-like disorder
Development of anxiety- and depression-like states under chronic social defeat stress in mice has been shown by many experimental studies. In this article, the differentially expressed Slc25* family genes encodin...
in Most Recent Articles: BMC Neuroscience on December 11, 2018 12:00 AM.
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Enzymatic and non-enzymatic pathways of kynurenines' dimerization: the molecular factors for oxidative stress development

by Aleksandr V. Zhuravlev, Oleg V. Vetrovoy, Elena V. Savvateeva-Popova
Kynurenines, the products of tryptophan oxidative degradation, are involved in multiple neuropathologies, such as Huntington's chorea, Parkinson's disease, senile dementia, etc. The major cause for hydroxykynurenines's neurotoxicity is the oxidative stress induced by the reactive oxygen species (ROS), the by-products of L-3-hydroxykynurenine (L-3HOK) and 3-hydroxyanthranilic acid (3HAA) oxidative self-dimerization. 2-aminophenol (2AP), a structural precursor of L-3HOK and 3HAA, undergoes the oxidative conjugation to form 2-aminophenoxazinone. There are several modes of 2AP dimerization, including both enzymatic and non-enzymatic stages. In this study, the free energies for 2AP, L-3HOK and 3HAA dimerization stages have been calculated at B3LYP/6-311G(d,p)//6-311+(O)+G(d) level, both in the gas phase and in heptane or water solution. For the intermediates, ionization potentials and electron affinities were calculated, as well as free energy and kinetics of molecular oxygen interaction with several non-enzymatically formed dimers. H-atom donating power of the intermediates increases upon the progress of the oxidation, making possible generation of hydroperoxyl radical or hydrogen peroxide from O₂ at the last stages. Among the dimerization intermediates, 2-aminophenoxazinole derivatives have the lowest ionization potential and can reduce O₂ to superoxide anion. The rate for O-H homolytic bond dissociation is significantly higher than that for C-H bond in non-enzymatic quinoneimine conjugate. However, the last reaction passes irreversibly, reducing O₂ to hydroperoxyl radical. The inorganic ferrous iron and the heme group of Drosophila phenoxazinone synthase significantly reduce the energy cost of 2AP H-atom abstraction by O₂. We have also shown experimentally that total antioxidant capacity decreases in Drosophila mutant cardinal with L-3HOK excess relative to the wild type Canton-S, and lipid peroxidation decreases in aged cardinal. Taken together, our data supports the conception of hydroxykynurenines' dual role in neurotoxicity: serving as antioxidants themselves, blocking lipid peroxidation by H-atom donation, they also can easily generate ROS upon dimerization, leading to the oxidative stress development.
in PLOS Computational Biology: New Articles on December 10, 2018 10:00 PM.
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Identifying (un)controllable dynamical behavior in complex networks

by Jordan C. Rozum, Réka Albert
We present a technique applicable in any dynamical framework to identify control-robust subsets of an interacting system. These robust subsystems, which we call stable modules, are characterized by constraints on the variables that make up the subsystem. They are robust in the sense that if the defining constraints are satisfied at a given time, they remain satisfied for all later times, regardless of what happens in the rest of the system, and can only be broken if the constrained variables are externally manipulated. We identify stable modules as graph structures in an expanded network, which represents causal links between variable constraints. A stable module represents a system “decision point”, or trap subspace. Using the expanded network, small stable modules can be composed sequentially to form larger stable modules that describe dynamics on the system level. Collections of large, mutually exclusive stable modules describe the system’s repertoire of long-term behaviors. We implement this technique in a broad class of dynamical systems and illustrate its practical utility via examples and algorithmic analysis of two published biological network models. In the segment polarity gene network of Drosophila melanogaster, we obtain a state-space visualization that reproduces by novel means the four possible cell fates and predicts the outcome of cell transplant experiments. In the T-cell signaling network, we identify six signaling elements that determine the high-signal response and show that control of an element connected to them cannot disrupt this response.
in PLOS Computational Biology: New Articles on December 10, 2018 10:00 PM.
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Coherency of circadian rhythms in the SCN is governed by the interplay of two coupling factors

by Isao T. Tokuda, Daisuke Ono, Sato Honma, Ken-Ichi Honma, Hanspeter Herzel
Circadian clocks are autonomous oscillators driving daily rhythms in physiology and behavior. In mammals, a network of coupled neurons in the suprachiasmatic nucleus (SCN) is entrained to environmental light-dark cycles and orchestrates the timing of peripheral organs. In each neuron, transcriptional feedbacks generate noisy oscillations. Coupling mediated by neuropeptides such as VIP and AVP lends precision and robustness to circadian rhythms. The detailed coupling mechanisms between SCN neurons are debated. We analyze organotypic SCN slices from neonatal and adult mice in wild-type and multiple knockout conditions. Different degrees of rhythmicity are quantified by pixel-level analysis of bioluminescence data. We use empirical orthogonal functions (EOFs) to characterize spatio-temporal patterns. Simulations of coupled stochastic single cell oscillators can reproduce the diversity of observed patterns. Our combination of data analysis and modeling provides deeper insight into the enormous complexity of the data: (1) Neonatal slices are typically stronger oscillators than adult slices pointing to developmental changes of coupling. (2) Wild-type slices are completely synchronized and exhibit specific spatio-temporal patterns of phases. (3) Some slices of Cry double knockouts obey impaired synchrony that can lead to co–existing rhythms (“splitting”). (4) The loss of VIP-coupling leads to desynchronized rhythms with few residual local clusters. Additional information was extracted from co–culturing slices with rhythmic neonatal wild-type SCNs. These co–culturing experiments were simulated using external forcing terms representing VIP and AVP signaling. The rescue of rhythmicity via co–culturing lead to surprising results, since a cocktail of AVP-antagonists improved synchrony. Our modeling suggests that these counter-intuitive observations are pointing to an antagonistic action of VIP and AVP coupling. Our systematic theoretical and experimental study shows that dual coupling mechanisms can explain the astonishing complexity of spatio-temporal patterns in SCN slices.
in PLOS Computational Biology: New Articles on December 10, 2018 10:00 PM.
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Odorant mixtures elicit less variable and faster responses than pure odorants

by Ho Ka Chan, Fabian Hersperger, Emiliano Marachlian, Brian H. Smith, Fernando Locatelli, Paul Szyszka, Thomas Nowotny
In natural environments, odors are typically mixtures of several different chemical compounds. However, the implications of mixtures for odor processing have not been fully investigated. We have extended a standard olfactory receptor model to mixtures and found through its mathematical analysis that odorant-evoked activity patterns are more stable across concentrations and first-spike latencies of receptor neurons are shorter for mixtures than for pure odorants. Shorter first-spike latencies arise from the nonlinear dependence of binding rate on odorant concentration, commonly described by the Hill coefficient, while the more stable activity patterns result from the competition between different ligands for receptor sites. These results are consistent with observations from numerical simulations and physiological recordings in the olfactory system of insects. Our results suggest that mixtures allow faster and more reliable olfactory coding, which could be one of the reasons why animals often use mixtures in chemical signaling.
in PLOS Computational Biology: New Articles on December 10, 2018 10:00 PM.
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Structural Changes Observed in the Piriform Cortex in a Rat Model of Pre-motor Parkinson’s Disease
Marco Sancandi, Emma Victoria Schul, Georgia Economides, Andrew Constanti, Audrey Mercer
in Frontiers in Cellular Neuroscience | New and Recent Articles on December 10, 2018 06:00 PM.
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An Automated Pipeline for the Analysis of PET Data on the Cortical Surface
Arnaud Marcoux, Ninon Burgos, Anne Bertrand, Marc Teichmann, Alexandre Routier, Junhao Wen, Jorge Samper-González, Simona Bottani, Stanley Durrleman, Marie-Odile Habert, Olivier Colliot, for the Alzheimer's Disease Neuroimaging Initiative
in Frontiers in Neuroinformatics | New and Recent Articles on December 10, 2018 06:00 PM.
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Lyme neuroborreliosis‐ clinical outcomes, controversy, pathogenesis, and polymicrobial infections

ABSTRACT

Lyme Borreliosis is the object of numerous misconceptions. In this review, we revisit the fundamental manifestations of neuroborreliosis (meningitis and cranial and radiculoneuritis) as these have withstood the test of time. We also discuss other manifestations that are less frequent. Stroke, as a manifestation of Lyme neuroborreliosis, is considered in the context of other infections. The summary of the literature regarding clinical outcomes of neuroborreliosis leads to its controversies. We also include new information on pathogenesis, and on the polymicrobial nature of tick‐borne diseases. In this way, we update the review that we wrote in this journal in 1995.

This article is protected by copyright. All rights reserved.

in Wiley: Annals of Neurology: Table of Contents on December 10, 2018 02:33 PM.
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The Role of Exercise-Induced Arousal and Exposure to Blue-Enriched Lighting on Vigilance
Antonio Barba, Francisca Padilla, Antonio Luque-Casado, Daniel Sanabria, Ángel Correa
in Frontiers in Human Neuroscience | New and Recent Articles on December 10, 2018 06:00 AM.
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Neural Correlates of Non-clinical Internet Use in the Motivation Network and Its Modulation by Subclinical Autistic Traits
Hironobu Fujiwara, Sayaka Yoshimura, Kei Kobayashi, Tsukasa Ueno, Naoya Oishi, Toshiya Murai
in Frontiers in Human Neuroscience | New and Recent Articles on December 10, 2018 06:00 AM.
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Comparison of fMRI Digit Representations of the Dominant and Non-dominant Hand in the Human Primary Somatosensory Cortex
Meike A. Schweisfurth, Jens Frahm, Dario Farina, Renate Schweizer
in Frontiers in Human Neuroscience | New and Recent Articles on December 10, 2018 06:00 AM.
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Short-Term Environmental Stimulation Spatiotemporally Modulates Specific Serotonin Receptor Gene Expression and Behavioral Pharmacology in a Sexually Dimorphic Manner in Huntington’s Disease Transgenic Mice
Michelle S. Zajac, Thibault Renoir, Victoria M. Perreau, Shanshan Li, Wendy Adams, Maarten van den Buuse, Anthony J. Hannan
in Frontiers in Molecular Neuroscience | New and Recent Articles on December 10, 2018 06:00 AM.
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Alterations of Graphic Properties and Related Cognitive Functioning Changes in Mild Alzheimer’s Disease Revealed by Individual Morphological Brain Network
Wan Li, Chunlan Yang, Shuicai Wu, Yingnan Nie, Xin Zhang, Ming Lu, Tongpeng Chu, Feng Shi
in Frontiers in Neuroscience | Neurodegeneration section | New and Recent Articles on December 10, 2018 06:00 AM.
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Increased Functional Connectivity Between Medulla and Inferior Parietal Cortex in Medication-Free Major Depressive Disorder
Lizhu Luo, Kunhua Wu, Yi Lu, Shan Gao, Xiangchao Kong, Fengmei Lu, Fengchun Wu, Huawang Wu, Jiaojian Wang
in Frontiers in Neuroscience | Brain Imaging Methods section | New and Recent Articles on December 10, 2018 06:00 AM.
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Epileptic Seizure Detection Based on EEG Signals and CNN
Mengni Zhou, Cheng Tian, Rui Cao, Bin Wang, Yan Niu, Ting Hu, Hao Guo, Jie Xiang
in Frontiers in Neuroinformatics | New and Recent Articles on December 10, 2018 06:00 AM.
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Brain Network Analysis and Classification Based on Convolutional Neural Network
Lu Meng, Jing Xiang
in Frontiers in Computational Neuroscience | New and Recent Articles on December 10, 2018 06:00 AM.
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Prediction of Autopsy Verified Neuropathological Change of Alzheimer’s Disease Using Machine Learning and MRI
Alexander Kautzky, Rene Seiger, Andreas Hahn, Peter Fischer, Wolfgang Krampla, Siegfried Kasper, Gabor G. Kovacs, Rupert Lanzenberger
in Frontiers in Aging Neuroscience | New and Recent Articles on December 10, 2018 06:00 AM.
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Trade-off between sensitivity and selectivity in systems with convergence. (arXiv:1812.03122v1 [q-bio.NC])

It was observed before that in neuronal systems with convergence, a possible amplification can be as large as the degree of convergence. This is in the case when a single impulse from the converging inputs is enough to trigger the secondary neuron. On the other hand, if a number of impulses are required for triggering, a gain in discriminating ability may be obtained along with decrease in sensitivity. We discuss this trade-off in terms of concrete estimates using olfactory sensory neuron and the set of its receptor proteins as an example of system with convergence.

in q-bio.NC updates on arXiv.org on December 10, 2018 01:30 AM.
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The Role of Engagement, Honing, and Mindfulness in Creativity. (arXiv:1812.02870v1 [q-bio.NC])

As both our external world and inner worlds become more complex, we are faced with more novel challenges, hardships, and duress. Creative thinking is needed to provide fresh perspectives and solve new problems.Because creativity can be conducive to accessing and reliving traumatic memories, emotional scars may be exacerbated by creative practices before these are transformed and released. Therefore, in preparing our youth to thrive in an increasingly unpredictable world, it could be helpful to cultivate in them an understanding of the creative process and its relationship to hardship, as well as tools and techniques for fostering not just creativity but self-awareness and mindfulness. This chapter is a review of theories of creativity through the lens of their capacity to account for the relationship between creativity and hardship, as well as the therapeutic effects of creativity. We also review theories and research on aspects of mindfulness attending to potential therapeutic effects of creativity. Drawing upon the creativity and mindfulness literatures, we sketch out what an introductory 'creativity and mindfulness' module might look like as part of an educational curriculum designed to address the unique challenges of the 21st Century.

in q-bio.NC updates on arXiv.org on December 10, 2018 01:30 AM.
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Role of astrocytes, microglia, and tanycytes in brain control of systemic metabolism

Role of astrocytes, microglia, and tanycytes in brain control of systemic metabolism
Role of astrocytes, microglia, and tanycytes in brain control of systemic metabolism, Published online: 10 December 2018; doi:10.1038/s41593-018-0286-y
Knowledge of the role of glial–neuronal interactions in the physiology of food intake and energy metabolism is emerging. This review highlights the role of astrocytes, microglia, and tanycytes in central control of systemic metabolism.
in Nature Neuroscience - Issue - nature.com science feeds on December 10, 2018 12:00 AM.
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Stimulus- and goal-oriented frameworks for understanding natural vision

Stimulus- and goal-oriented frameworks for understanding natural vision
Stimulus- and goal-oriented frameworks for understanding natural vision, Published online: 10 December 2018; doi:10.1038/s41593-018-0284-0
A satisfactory understanding of how natural stimuli are encoded by neural circuits has remained elusive. Advances in machine learning provide new approaches to this problem by merging constraints imposed by stimulus statistics and behavioral goals.
in Nature Neuroscience - Issue - nature.com science feeds on December 10, 2018 12:00 AM.
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CaV2.1 α1 Subunit Expression Regulates Presynaptic CaV2.1 Abundance and Synaptic Strength at a Central Synapse
Lübbert et al. uncover that presynaptic active zones are not fully occupied by CaV2.1 during different states of neuronal circuit maturity. They propose that CaV2.1 levels in the presynaptic active zone can be increased to regulate neuronal circuit output.
in Neuron on December 10, 2018 12:00 AM.
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Predicting protein targets for drug-like compounds using transcriptomics

by Nicolas A. Pabon, Yan Xia, Samuel K. Estabrooks, Zhaofeng Ye, Amanda K. Herbrand, Evelyn Süß, Ricardo M. Biondi, Victoria A. Assimon, Jason E. Gestwicki, Jeffrey L. Brodsky, Carlos J. Camacho, Ziv Bar-Joseph
An expanded chemical space is essential for improved identification of small molecules for emerging therapeutic targets. However, the identification of targets for novel compounds is biased towards the synthesis of known scaffolds that bind familiar protein families, limiting the exploration of chemical space. To change this paradigm, we validated a new pipeline that identifies small molecule-protein interactions and works even for compounds lacking similarity to known drugs. Based on differential mRNA profiles in multiple cell types exposed to drugs and in which gene knockdowns (KD) were conducted, we showed that drugs induce gene regulatory networks that correlate with those produced after silencing protein-coding genes. Next, we applied supervised machine learning to exploit drug-KD signature correlations and enriched our predictions using an orthogonal structure-based screen. As a proof-of-principle for this regimen, top-10/top-100 target prediction accuracies of 26% and 41%, respectively, were achieved on a validation set 152 FDA-approved drugs and 3104 potential targets. We then predicted targets for 1680 compounds and validated chemical interactors with four targets that have proven difficult to chemically modulate, including non-covalent inhibitors of HRAS and KRAS. Importantly, drug-target interactions manifest as gene expression correlations between drug treatment and both target gene KD and KD of genes that act up- or down-stream of the target, even for relatively weak binders. These correlations provide new insights on the cellular response of disrupting protein interactions and highlight the complex genetic phenotypes of drug treatment. With further refinement, our pipeline may accelerate the identification and development of novel chemical classes by screening compound-target interactions.
in PLOS Computational Biology: New Articles on December 07, 2018 10:00 PM.
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Projecting social contact matrices to different demographic structures

by Sergio Arregui, Alberto Aleta, Joaquín Sanz, Yamir Moreno
The modeling of large-scale communicable epidemics has greatly benefited in the last years from the increasing availability of highly detailed data. Particullarly, in order to achieve quantitative descriptions of the evolution of epidemics, contact networks and mixing patterns are key. These heterogeneous patterns depend on several factors such as location, socioeconomic conditions, time, and age. This last factor has been shown to encapsulate a large fraction of the observed inter-individual variation in contact patterns, an observation validated by different measurements of age-dependent contact matrices. Recently, several works have studied how to project those matrices to areas where empirical data are not available. However, the dependence of contact matrices on demographic structures and their time evolution has been largely neglected. In this work, we tackle the problem of how to transform an empirical contact matrix that has been obtained for a given demographic structure into a different contact matrix that is compatible with a different demography. The methodology discussed here allows to extrapolate a contact structure measured in a particular area to any other whose demographic structure is known, as well as to obtain the time evolution of contact matrices as a function of the demographic dynamics of the populations they refer to. To quantify the effect of considering time-dynamics of contact patterns on disease modeling, we implemented a Susceptible-Exposed-Infected-Recovered (SEIR) model on 16 different countries and regions and evaluated the impact of neglecting the temporal evolution of mixing patterns. Our results show that simulated disease incidence rates, both at the aggregated and age-specific levels, are significantly dependent on contact structures variation driven by demographic evolution. The present work opens the path to eliminate technical biases from model-based impact evaluations of future epidemic threats and warns against the use of contact matrices to model diseases without correcting for demographic evolution or geographic variations.
in PLOS Computational Biology: New Articles on December 07, 2018 10:00 PM.
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PathFX provides mechanistic insights into drug efficacy and safety for regulatory review and therapeutic development

by Jennifer L. Wilson, Rebecca Racz, Tianyun Liu, Oluseyi Adeniyi, Jielin Sun, Anuradha Ramamoorthy, Michael Pacanowski, Russ Altman
Failure to demonstrate efficacy and safety issues are important reasons that drugs do not reach the market. An incomplete understanding of how drugs exert their effects hinders regulatory and pharmaceutical industry projections of a drug’s benefits and risks. Signaling pathways mediate drug response and while many signaling molecules have been characterized for their contribution to disease or their role in drug side effects, our knowledge of these pathways is incomplete. To better understand all signaling molecules involved in drug response and the phenotype associations of these molecules, we created a novel method, PathFX, a non-commercial entity, to identify these pathways and drug-related phenotypes. We benchmarked PathFX by identifying drugs’ marketed disease indications and reported a sensitivity of 41%, a 2.7-fold improvement over similar approaches. We then used PathFX to strengthen signals for drug-adverse event pairs occurring in the FDA Adverse Event Reporting System (FAERS) and also identified opportunities for drug repurposing for new diseases based on interaction paths that associated a marketed drug to that disease. By discovering molecular interaction pathways, PathFX improved our understanding of drug associations to safety and efficacy phenotypes. The algorithm may provide a new means to improve regulatory and therapeutic development decisions.
in PLOS Computational Biology: New Articles on December 07, 2018 10:00 PM.
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Deep convolutional networks do not classify based on global object shape

by Nicholas Baker, Hongjing Lu, Gennady Erlikhman, Philip J. Kellman
Deep convolutional networks (DCNNs) are achieving previously unseen performance in object classification, raising questions about whether DCNNs operate similarly to human vision. In biological vision, shape is arguably the most important cue for recognition. We tested the role of shape information in DCNNs trained to recognize objects. In Experiment 1, we presented a trained DCNN with object silhouettes that preserved overall shape but were filled with surface texture taken from other objects. Shape cues appeared to play some role in the classification of artifacts, but little or none for animals. In Experiments 2–4, DCNNs showed no ability to classify glass figurines or outlines but correctly classified some silhouettes. Aspects of these results led us to hypothesize that DCNNs do not distinguish object’s bounding contours from other edges, and that DCNNs access some local shape features, but not global shape. In Experiment 5, we tested this hypothesis with displays that preserved local features but disrupted global shape, and vice versa. With disrupted global shape, which reduced human accuracy to 28%, DCNNs gave the same classification labels as with ordinary shapes. Conversely, local contour changes eliminated accurate DCNN classification but caused no difficulty for human observers. These results provide evidence that DCNNs have access to some local shape information in the form of local edge relations, but they have no access to global object shapes.
in PLOS Computational Biology: New Articles on December 07, 2018 10:00 PM.
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Multi-scale computational study of the Warburg effect, reverse Warburg effect and glutamine addiction in solid tumors

by Mengrou Shan, David Dai, Arunodai Vudem, Jeffrey D. Varner, Abraham D. Stroock
Cancer metabolism has received renewed interest as a potential target for cancer therapy. In this study, we use a multi-scale modeling approach to interrogate the implications of three metabolic scenarios of potential clinical relevance: the Warburg effect, the reverse Warburg effect and glutamine addiction. At the intracellular level, we construct a network of central metabolism and perform flux balance analysis (FBA) to estimate metabolic fluxes; at the cellular level, we exploit this metabolic network to calculate parameters for a coarse-grained description of cellular growth kinetics; and at the multicellular level, we incorporate these kinetic schemes into the cellular automata of an agent-based model (ABM), iDynoMiCS. This ABM evaluates the reaction-diffusion of the metabolites, cellular division and motion over a simulation domain. Our multi-scale simulations suggest that the Warburg effect provides a growth advantage to the tumor cells under resource limitation. However, we identify a non-monotonic dependence of growth rate on the strength of glycolytic pathway. On the other hand, the reverse Warburg scenario provides an initial growth advantage in tumors that originate deeper in the tissue. The metabolic profile of stromal cells considered in this scenario allows more oxygen to reach the tumor cells in the deeper tissue and thus promotes tumor growth at earlier stages. Lastly, we suggest that glutamine addiction does not confer a selective advantage to tumor growth with glutamine acting as a carbon source in the tricarboxylic acid (TCA) cycle, any advantage of glutamine uptake must come through other pathways not included in our model (e.g., as a nitrogen donor). Our analysis illustrates the importance of accounting explicitly for spatial and temporal evolution of tumor microenvironment in the interpretation of metabolic scenarios and hence provides a basis for further studies, including evaluation of specific therapeutic strategies that target metabolism.
in PLOS Computational Biology: New Articles on December 07, 2018 10:00 PM.
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Stroke recovery in rats after 24h‐delayed, intramuscular neurotrophin‐3 infusion

Abstract

Objectives

Neurotrophin‐3 (NT3) plays a key role in the development and function of locomotor circuits including descending serotonergic and corticospinal tract (CST) axons and afferents from muscle and skin. We have previously shown that gene therapy delivery of human NT3 into affected forelimb muscles improves sensorimotor recovery after stroke in adult and elderly rats. Here, to move towards the clinic, we tested the hypothesis that intramuscular infusion of NT3 protein could improve sensorimotor recovery after stroke.

Methods

Rats received unilateral ischemic stroke in sensorimotor cortex. To simulate a clinically‐feasible time‐to‐treat, twenty‐four hours later rats were randomized to receive NT3 or vehicle by infusion into affected triceps brachii for four weeks using implanted catheters and minipumps.

Results

Radiolabelled NT3 crossed from the bloodstream into the brain and spinal cord in rodents with or without strokes. NT3 increased the accuracy of forelimb placement during walking on a horizontal ladder and increased use of the affected arm for lateral support during rearing. NT3 also reversed sensory impairment of the affected wrist. fMRI during stimulation of the affected wrist showed spontaneous recovery of peri‐infarct BOLD signal that NT3 did not further enhance. Rather, NT3 induced neuroplasticity of the spared corticospinal and serotonergic pathways.

Interpretation

Our results show that delayed, peripheral infusion of NT3 can improve sensorimotor function after ischemic stroke. Phase I and II clinical trials of NT3 (for constipation and neuropathy) have shown that peripheral, high doses are safe and well tolerated, which paves the way for NT3 as a therapy for stroke.

This article is protected by copyright. All rights reserved.

in Wiley: Annals of Neurology: Table of Contents on December 07, 2018 08:00 PM.
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Neuronal identity: the neuron types of a simple chordate sibling, the tadpole larva of Ciona intestinalis

Publication date: June 2019
Source: Current Opinion in Neurobiology, Volume 56
Author(s): Kerrianne Ryan, Ian A Meinertzhagen
Neurons of the sparsely populated nervous system of the tadpole larva in the tunicate Ciona intestinalis, a chordate sibling, are known from sporadic previous studies but especially two recent reports that document the connectome of both the central and peripheral nervous systems at EM level. About 330 CNS cells comprise mostly ciliated ependymal cells, with ∼180 neurons that constitute about 50 morphologically distinguishable types. The neurons reveal various chordate characters amid many features that are idiosyncratic. Most neurons are ciliated and lack dendrites, some even lack an axon. Synapses mostly form en passant between axons, and resemble those in basal invertebrates; some are dyads and all have heterogenous synaptic vesicle populations. Each neuron has on average 49 synapses with other cells; these constitute a synaptic network of unpredicted complexity.

in ScienceDirect Publication: Current Opinion in Neurobiology on December 07, 2018 06:00 PM.
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The algorithmic architecture of exploration in the human brain

Publication date: April 2019
Source: Current Opinion in Neurobiology, Volume 55
Author(s): Eric Schulz, Samuel J. Gershman
Balancing exploration and exploitation is one of the central problems in reinforcement learning. We review recent studies that have identified multiple algorithmic strategies underlying exploration. In particular, humans use a combination of random and uncertainty-directed exploration strategies, which rely on different brain systems, have different developmental trajectories, and are sensitive to different task manipulations. Humans are also able to exploit sophisticated structural knowledge to aid their exploration, such as information about correlations between options. New computational models, drawing inspiration from machine learning, have begun to formalize these ideas and offer new ways to understand the neural basis of reinforcement learning.

in ScienceDirect Publication: Current Opinion in Neurobiology on December 07, 2018 06:00 PM.
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Perspectives on defining cell types in the brain

Publication date: June 2019
Source: Current Opinion in Neurobiology, Volume 56
Author(s): Eran A Mukamel, John Ngai
The diversity of brain cell types was one of the earliest observations in modern neuroscience and continues to be one of the central concerns of current neuroscience research. Despite impressive recent progress, including single cell transcriptome and epigenome profiling as well as anatomical methods, we still lack a complete census or taxonomy of brain cell types. We argue this is due partly to the conceptual difficulty in defining a cell type. By considering the biological drivers of cell identity, such as networks of genes and gene regulatory elements, we propose a definition of cell type that emphasizes self-stabilizing regulation. We explore the predictions and hypotheses that arise from this definition. Integration of data from multiple modalities, including molecular profiling of genes and gene products, epigenetic landscape, cellular morphology, connectivity, and physiology, will be essential for a meaningful and broadly useful definition of brain cell types.

in ScienceDirect Publication: Current Opinion in Neurobiology on December 07, 2018 06:00 PM.
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Electrophysiological correlates of absolute pitch in a passive auditory oddball paradigm: a direct replication attempt
Abstract
Humans with absolute pitch (AP) are able to effortlessly name the pitch class of a sound without an external reference. The association of labels with pitches cannot be entirely suppressed even if it interferes with task demands. This suggests a high level of automaticity of pitch labeling in AP. The automatic nature of AP was further investigated in a study by Rogenmoser et al. (2015). Using a passive auditory oddball paradigm in combination with electroencephalography, they observed electrophysiological differences between musicians with and without AP in response to piano tones. Specifically, the AP musicians showed a smaller P3a, an event-related potential (ERP) component presumably reflecting early attentional processes. In contrast, they did not find group differences in the mismatch negativity (MMN), an ERP component associated with auditory memory processes. They concluded that early cognitive processes are facilitated in AP during passive listening and are more important for AP than the preceding sensory processes.
In our direct replication study on a larger sample of musicians with (n = 54, 27 females, 27 males) and without (n = 50, 24 females, 26 males) AP, we successfully replicated the non-significant effects of AP on the MMN. However, we could not replicate the significant effects for the P3a. Additional Bayes factor analyses revealed moderate to strong evidence (Bayes factor > 3) for the null hypothesis for both MMN and P3a. Therefore, the results of this replication study do not support the postulated importance of cognitive facilitation in AP during passive tone listening.
Significance Statement A better understanding of the neural basis of absolute pitch (AP), the ability to identify a pitch without an external reference, provides valuable insights to the mechanisms of pitch processing in the human brain. Since only a tiny fraction of the population possesses AP, most previous neuroscientific research had small sample sizes. In our direct replication, we used a large sample of musicians (n = 104) with and without AP to confirm an intriguing finding showing that AP musicians process tones more efficiently even when not actively attending them. Using both frequentist and Bayesian analyses, we failed to replicate this effect with an identical experimental setting. This finding highlights the significance of replications and the need for large sample sizes.

in RSS PAP on December 07, 2018 05:40 PM.
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The Mixed-Lineage Kinase Inhibitor URMC-099 Protects Hippocampal Synapses in Experimental Autoimmune Encephalomyelitis
Abstract
Treatments to stop gray matter degeneration are needed to prevent progressive disability in multiple sclerosis (MS). We tested whether inhibiting mixed-lineage kinases (MLKs), which can drive inflammatory microglial activation and neuronal degeneration, could protect hippocampal synapses in C57BL/6 mice with experimental autoimmune encephalomyelitis (EAE), a disease model that recapitulates the excitatory synaptic injury that occurs widely within the gray matter in MS. URMC-099, a broad spectrum MLK inhibitor with additional activity against leucine-rich repeat kinase 2 (LRRK2) and other kinases, prevented loss of PSD95-positive postsynaptic structures, shifted activated microglia toward a less inflammatory phenotype, and reversed deficits in hippocampal-dependent contextual fear conditioning in EAE mice when administered after the onset of motor symptoms. A narrow spectrum inhibitor designed to be highly selective for MLK3 failed to protect synapses in EAE hippocampi, and could not rescue cultured neurons from trophic deprivation in an in vitro model of MLK-driven neuronal degeneration. These results suggest that URMC-099 may have potential as a neuroprotective treatment in MS and demonstrate that a broad spectrum of inhibition against a combination of MLK and other kinases is more effective in neuroinflammatory disease than selectively targeting a single kinase.

in eNeuro current issue on December 07, 2018 05:28 PM.
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Long-Term Potentiation and Excitability in the Hippocampus Are Modulated Differently by {theta} Rhythm

Oscillations in the brain facilitate neural processing and cognitive functions. This study investigated the dependence of long-term potentiation (LTP), a neural correlate of memory, on the phase of the hippocampal rhythm, a prominent brain oscillation. Multichannel field potentials and current source-sinks were analyzed in hippocampal CA1 of adult male rats under urethane anesthesia. A single burst (five pulses at 200 Hz) stimulation of stratum oriens (OR) induced LTP of the basal dendritic excitatory sink (ES), which was maximal when the burst was delivered at ~340° and ~160° of the distal dendritic rhythm. Apical dendritic sink evoked by stratum radiatum (RAD) stimulation also showed biphasic maxima at ~30° and ~210° of the distal dendritic rhythm, about 50° phase delay to basal dendritic LTP. By contrast, maximal population spike (PS) excitability, following single-pulse excitation of the basal or mid-apical dendrites, occurred at a phase of ~140°, and maximal basal dendritic ES occurred at ~20°; (30–57 Hz) activity recorded in CA1 RAD had maximal power at ~300° of the distal dendritic rhythm, different from the phases of maximal LTP. LTP induced during the rising phase was NMDA receptor sensitive. It is suggested that the phase modulation of CA1 PS excitability is mainly provided by -rhythmic proximal inhibition, while dendritic LTP is also modulated by dendritic inhibition and excitation, specific to basal and apical dendrites. In summary, basal and apical dendritic synaptic plasticity and spike excitability are facilitated at different phases in a compartmental fashion.

in eNeuro current issue on December 07, 2018 05:28 PM.
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Insula as the Interface Between Body Awareness and Movement: A Neurofeedback-Guided Kinesthetic Motor Imagery Study in Parkinson’s Disease
Sule Tinaz, Kiran Para, Ana Vives-Rodriguez, Valeria Martinez-Kaigi, Keerthana Nalamada, Mine Sezgin, Dustin Scheinost, Michelle Hampson, Elan D. Louis, R. Todd Constable
in Frontiers in Human Neuroscience | New and Recent Articles on December 07, 2018 06:00 AM.
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Adenosine Actions on Oligodendroglia and Myelination in Autism Spectrum Disorder
Hai-Ying Shen, Nanxin Huang, Jesica Reemmer, Lan Xiao
in Frontiers in Cellular Neuroscience | New and Recent Articles on December 07, 2018 06:00 AM.
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Non-parametric Physiological Classification of Retinal Ganglion Cells in the Mouse Retina
Jonathan Jouty, Gerrit Hilgen, Evelyne Sernagor, Matthias H. Hennig
in Frontiers in Cellular Neuroscience | New and Recent Articles on December 07, 2018 06:00 AM.
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Methyl 3,4-Dihydroxybenzoate Induces Neural Stem Cells to Differentiate Into Cholinergic Neurons in vitro
Jun-Ping Pan, Yang Hu, Jia-Hui Wang, Yi-Rong Xin, Jun-Xing Jiang, Ke-Qi Chen, Cheng-You Yang, Qin Gao, Fei Xiao, Li Yan, Huan-Min Luo
in Frontiers in Cellular Neuroscience | New and Recent Articles on December 07, 2018 06:00 AM.
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Dysregulation of the Lateral Habenula in Major Depressive Disorder
Caroline A. Browne, Robert Hammack, Irwin Lucki
in Frontiers in Synaptic Neuroscience | New and Recent Articles on December 07, 2018 06:00 AM.
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From Matrices to Knowledge: Using Semantic Networks to Annotate the Connectome
Sebastian J. Kopetzky, Markus Butz-Ostendorf
in Frontiers in Neuroanatomy | New and Recent Articles on December 07, 2018 06:00 AM.
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Identification of PSD-95 in the Postsynaptic Density Using MiniSOG and EM Tomography
Xiaobing Chen, Christine Winters, Virginia Crocker, Michael Lazarou, Alioscka A. Sousa, Richard D. Leapman, Thomas S. Reese
in Frontiers in Neuroanatomy | New and Recent Articles on December 07, 2018 06:00 AM.
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Perceptual reversals in binocular rivalry: improved detection from OKN. (arXiv:1812.02478v1 [q-bio.NC])

When binocular rivalry is induced by opponent motion displays, perceptual reversals are often associated with changed oculomotor behaviour (Frassle et al., 2014; Fujiwara et al., 2017). Specifically, the direction of smooth pursuit phases in optokinetic nystagmus (OKN) typically corresponds to the direction of motion that dominates perceptual appearance at any given time. Here we report an improved analysis that continuously estimates perceived motion in terms of `cumulative smooth pursuit'. In essence, smooth pursuit segments are identified, interpolated where necessary, and joined probabilistically into a continuous record of `cumulative smooth pursuit' (i.e., a probability of eye position disregarding blinks, saccades, signal losses, and artefacts). The analysis is fully automated and robust in healthy, developmental, and patient populations. To validate reliability, we compare volitional reports of perceptual reversals in rivalry displays, and of physical reversals in non-rivalrous control displays. `Cumulative smooth pursuit' detects physical reversals and estimates eye velocity more accurately than existing methods do (Frassle et al., 2014). It also appears to distinguish dominant and transitional perceptual states, detecting changes with a precision of $\pm100\,\mathit{ms}$. We conclude that `cumulative smooth pursuit' significantly improves the monitoring of binocular rivalry by means of recording OKN.

in q-bio.NC updates on arXiv.org on December 07, 2018 01:30 AM.
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Educational Implications of the 'Self-Made Worldview' Concept. (arXiv:1812.02338v1 [q-bio.NC])

Immersion in a creative task can be an intimate experience. It can feel like a mystery: intangible, inexplicable, and beyond the reach of science. However, science is making exciting headway into understanding creativity. While the mind of a highly uncreative individual consists of a collection of items accumulated through direct experience and enculturation, the mind of a creative individual is self-organizing and self-mending; thus, experiences and items of cultural knowledge are thought through from different perspectives such that they cohere together into a loosely integrated whole. The reweaving of items in memory is elicited by perturbations: experiences that increase psychological entropy because they are inconsistent with one's web of understandings. The process of responding to one perturbation often leads to other perturbations, i.e., other inconsistencies in one's web of understandings. Creative thinking often requires the capacity to shift between divergent and convergent modes of thought in response to the ever-changing demands of the creative task. Since uncreative individuals can reap the benefits of creativity by imitating creators, using their inventions, or purchasing their artworks, it is not necessary that everyone be creative. Agent based computer models of cultural evolution suggest that society functions best with a mixture of creative and uncreative individuals. The ideal ratio of creativity to imitation increases in times of change, such as we are experiencing now. Therefore it is important to educate the next generation in ways that foster creativity. The chapter concludes with suggestions for how educational systems can cultivate creativity.

in q-bio.NC updates on arXiv.org on December 07, 2018 01:30 AM.
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Detecting Epileptic Seizures from EEG Data using Neural Networks. (arXiv:1412.6502v5 [cs.LG] UPDATED)

We explore the use of neural networks trained with dropout in predicting epileptic seizures from electroencephalographic data (scalp EEG). The input to the neural network is a 126 feature vector containing 9 features for each of the 14 EEG channels obtained over 1-second, non-overlapping windows. The models in our experiments achieved high sensitivity and specificity on patient records not used in the training process. This is demonstrated using leave-one-out-cross-validation across patient records, where we hold out one patient's record as the test set and use all other patients' records for training; repeating this procedure for all patients in the database.

in q-bio.NC updates on arXiv.org on December 07, 2018 01:30 AM.
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Astrocyte identity: evolutionary perspectives on astrocyte functions and heterogeneity

Publication date: June 2019
Source: Current Opinion in Neurobiology, Volume 56
Author(s): Yongjie Yang, Rob Jackson
The development of new animal models, in vivo isolation approaches, and improvements in genome-wide RNA expression methods have greatly propelled molecular profiling of astrocytes and the characterization of astrocyte heterogeneity in the central nervous system (CNS). Several recent reviews have comprehensively discussed the molecular and functional diversity of mammalian astrocytes. In this brief review, we emphasize interspecies comparisons and an evolutionary perspective regarding the astro(glia) of vertebrates and invertebrates which are similar in form and function. This analysis has revealed conserved astrocyte transcriptomes in the fly, mouse and human. We also offer opinions about the pattern and origin of astrocyte heterogeneity in the CNS.

in ScienceDirect Publication: Current Opinion in Neurobiology on December 07, 2018 12:00 AM.
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Emergence of Coordinated Activity in the Developing Entorhinal–Hippocampal Network

Abstract
Correlated activity in the entorhinal–hippocampal neuronal networks, supported by oscillatory and intermittent population activity patterns is critical for learning and memory. However, when and how correlated activity emerges in these networks during development remains largely unknown. Here, we found that during the first postnatal week in non-anaesthetized head-restrained rats, activity in the superficial layers of the medial entorhinal cortex (MEC) and hippocampus was highly correlated, with intermittent population bursts in the MEC followed by early sharp waves (eSPWs) in the hippocampus. Neurons in the superficial MEC layers fired before neurons in the dentate gyrus, CA3 and CA1. eSPW current-source density profiles indicated that perforant/temporoammonic entorhinal inputs and intrinsic hippocampal connections are co-activated during entorhinal–hippocampal activity bursts. Finally, a majority of the entorhinal–hippocampal bursts were triggered by spontaneous myoclonic body movements, characteristic of the neonatal period. Thus, during the neonatal period, activity in the entorhinal cortex (EC) and hippocampus is highly synchronous, with the EC leading hippocampal activation. We propose that such correlated activity is embedded into a large-scale bottom-up circuit that processes somatosensory feedback resulting from neonatal movements, and that it is likely to instruct the development of connections between neocortex and hippocampus.
in Cerebral Cortex Advance Access on December 07, 2018 12:00 AM.
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Direct and Collateral Alterations of Functional Cortical Circuits in a Rat Model of Subcortical Band Heterotopia

Abstract
Subcortical band heterotopia (SBH), also known as double-cortex syndrome, is a neuronal migration disorder characterized by an accumulation of neurons in a heterotopic band below the normotopic cortex. The majority of patients with SBH have mild to moderate intellectual disability and intractable epilepsy. However, it is still not clear how cortical networks are organized in SBH patients and how this abnormal organization contributes to improper brain function. In this study, cortical networks were investigated in the barrel cortex in an animal model of SBH induced by in utero knockdown of Dcx, main causative gene of this condition in human patients. When the SBH was localized below the Barrel Field (BF), layer (L) four projection to correctly positioned L2/3 pyramidal cells was weakened due to lower connectivity. Conversely, when the SBH was below an adjacent cortical region, the excitatory L4 to L2/3 projection was stronger due to increased L4 neuron excitability, synaptic strength and excitation/inhibition ratio of L4 to L2/3 connection. We propose that these developmental alterations contribute to the spectrum of clinical dysfunctions reported in patients with SBH.
in Cerebral Cortex Advance Access on December 07, 2018 12:00 AM.
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Neurons in the Macaque Dorsal Premotor Cortex Respond to Execution and Observation of Actions

Abstract
We identified neurons in dorsal premotor cortex (PMd) of the macaque brain that respond during execution and observation of reaching-to-grasp actions, thus fulfilling the mirror neuron (MirN) criterion. During observation, the percentage of grip-selective MirNs in PMd and area F5 were comparable, and the selectivity indices in the two areas were similar. During execution, F5-MirNs were more selective than PMd–MirNs for grip, which was reflected in the higher selectivity indices in F5 than in PMd. PMd displayed grip-related information earlier than F5 during both conditions. In both areas, the number of neurons exhibiting congruent visual and motor selectivity did not differ from that expected by chance. However, both the PMd and F5 neuronal ensembles provided observation–execution matching, suggesting that the congruency may be achieved in a distributed fashion across the selective elements of the population. Furthermore, representational similarity analysis revealed that grip encoding in PMd and F5 is alike during both observation and execution. Our study provides direct evidence of mirror activity in PMd during observation of forelimb movements, and suggests that PMd is a node of the MirN circuit.
in Cerebral Cortex Advance Access on December 07, 2018 12:00 AM.
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Development and Emergence of Individual Variability in the Functional Connectivity Architecture of the Preterm Human Brain

Abstract
Individual variability in human brain networks underlies individual differences in cognition and behaviors. However, researchers have not conclusively determined when individual variability patterns of the brain networks emerge and how they develop in the early phase. Here, we employed resting-state functional MRI data and whole-brain functional connectivity analyses in 40 neonates aged around 31–42 postmenstrual weeks to characterize the spatial distribution and development modes of individual variability in the functional network architecture. We observed lower individual variability in primary sensorimotor and visual areas and higher variability in association regions at the third trimester, and these patterns are generally similar to those of adult brains. Different functional systems showed dramatic differences in the development of individual variability, with significant decreases in the sensorimotor network; decreasing trends in the visual, subcortical, and dorsal and ventral attention networks, and limited change in the default mode, frontoparietal and limbic networks. The patterns of individual variability were negatively correlated with the short- to middle-range connection strength/number and this distance constraint was significantly strengthened throughout development. Our findings highlight the development and emergence of individual variability in the functional architecture of the prenatal brain, which may lay network foundations for individual behavioral differences later in life.
in Cerebral Cortex Advance Access on December 07, 2018 12:00 AM.
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Age-Related Differences in Brain Morphology and the Modifiers in Middle-Aged and Older Adults

Abstract
Brain structural morphology differs with age. This study examined age-differences in surface-based morphometric measures of cortical thickness, volume, and surface area in a well-defined sample of 8137 generally healthy UK Biobank participants aged 45–79 years. We illustrate that the complexity of age-related brain morphological differences may be related to the laminar organization and regional evolutionary history of the cortex, and age of about 60 is a break point for increasing negative associations between age and brain morphology in Alzheimer’s disease (AD)-prone areas. We also report novel relationships of age-related cortical differences with individual factors of sex, cognitive functions of fluid intelligence, reaction time and prospective memory, cigarette smoking, alcohol consumption, sleep disruption, genetic markers of apolipoprotein E, brain-derived neurotrophic factor, catechol-O-methyltransferase, and several genome-wide association study loci for AD and further reveal joint effects of cognitive functions, lifestyle behaviors, and education on age-related cortical differences. These findings provide one of the most extensive characterizations of age associations with major brain morphological measures and improve our understanding of normal structural brain aging and its potential modifiers.
in Cerebral Cortex Advance Access on December 07, 2018 12:00 AM.
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Dorsolateral Prefrontal Cortex Enables Updating of Established Memories

Abstract
Updating established memories in light of new information is fundamental for memory to guide future behavior. However, little is known about the brain mechanisms by which existing memories can be updated. Here, we combined functional magnetic resonance imaging and multivariate representational similarity analysis to elucidate the neural mechanisms underlying the updating of consolidated memories. To this end, participants first learned face–city name pairs. Twenty-four hours later, while lying in the MRI scanner, participants were required to update some of these associations, but not others, and to encode entirely new pairs. Updating success was tested again 24 h later. Our results showed increased activity of the dorsolateral prefrontal cortex (dlPFC) specifically during the updating of existing associations that was significantly stronger than when simple retrieval or new encoding was required. The updating-related activity of the dlPFC and its functional connectivity with the hippocampus were directly linked to updating success. Furthermore, neural similarity for updated items was markedly higher in the dlPFC and this increase in dlPFC neural similarity distinguished individuals with high updating performance from those with low updating performance. Together, these findings suggest a key role of the dlPFC, presumably in interaction with the hippocampus, in the updating of established memories.
in Cerebral Cortex Advance Access on December 07, 2018 12:00 AM.
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Early Loss of Vision Results in Extensive Reorganization of Plasticity-Related Receptors and Alterations in Hippocampal Function That Extend Through Adulthood

Abstract
Although by adulthood cortical structures and their capacity for processing sensory information have become established and stabilized, under conditions of cortical injury, or sensory deprivation, rapid reorganization occurs. Little is known as to the impact of this kind of adaptation on cellular processes related to memory encoding. However, imaging studies in humans suggest that following loss or impairment of a sensory modality, not only cortical but also subcortical structures begin to reorganize. It is likely that these processes are supported by neurotransmitter receptors that enable synaptic and cortical plasticity. Here, we explored to what extent the expression of plasticity-related proteins (GABA-A, GABA-B, GluN1, GluN2A, GluN2B) is altered following early vision loss, and whether this impacts on hippocampal function. We observed that in the period of 2–4 months postnatally in CBA/J-mice that experience hereditary postnatal retinal degeneration, systematic changes of GABA-receptor and NMDA-receptor subunit expression occurred that emerged first in the hippocampus and developed later in the cortex, compared to control mice that had normal vision. Changes were accompanied by significant impairments in hippocampal long-term potentiation and hippocampus-dependent learning. These data indicate that during cortical adaptation to early loss of vision, hippocampal information processing is compromised, and this status impacts on the acquisition of spatial representations.
in Cerebral Cortex Advance Access on December 07, 2018 12:00 AM.
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Lesions to the Fronto-Parietal Network Impact Alpha-Band Phase Synchrony and Cognitive Control

Abstract
Long-range phase synchrony in the α-oscillation band (near 10 Hz) has been proposed to facilitate information integration across anatomically segregated regions. Which areas may top-down regulate such cross-regional integration is largely unknown. We previously found that the moment-to-moment strength of high-α band (10–12 Hz) phase synchrony co-varies with activity in a fronto-parietal (FP) network. This network is critical for adaptive cognitive control functions such as cognitive flexibility required during set-shifting. Using electroencephalography (EEG) in 23 patients with focal frontal lobe lesions (resected tumors), we tested the hypothesis that the FP network is necessary for modulation of high-α band phase synchrony. Global phase-synchrony was measured using an adaptation of the phase-locking value (PLV) in a sliding window procedure, which allowed for measurement of changes in EEG-based resting-state functional connectivity across time. As hypothesized, the temporal modulation (range and standard deviation) of high-α phase synchrony was reduced as a function of FP network lesion extent, mostly due to dorsolateral prefrontal cortex (dlPFC) lesions. Furthermore, patients with dlPFC lesions exhibited reduced cognitive flexibility as measured by the Trail-Making Test (set-shifting). Our findings provide evidence that the FP network is necessary for modulatory control of high-α band long-range phase synchrony, and linked to cognitive flexibility.
in Cerebral Cortex Advance Access on December 07, 2018 12:00 AM.
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Oxytocin Modulates the Intrinsic Dynamics Between Attention-Related Large-Scale Networks

Abstract
Attention and salience processing have been linked to the intrinsic between- and within-network dynamics of large-scale networks engaged in internal (default network [DN]) and external attention allocation (dorsal attention network [DAN] and salience network [SN]). The central oxytocin (OXT) system appears ideally organized to modulate widely distributed neural systems and to regulate the switch between internal attention and salient stimuli in the environment. The current randomized placebo (PLC)-controlled between-subject pharmacological resting-state fMRI study in N = 187 (OXT, n = 94; PLC, n = 93; single-dose intranasal administration) healthy male and female participants employed an independent component analysis approach to determine the modulatory effects of OXT on the within- and between-network dynamics of the DAN–SN–DN triple network system. OXT increased the functional integration between subsystems within SN and DN and increased functional segregation of the DN with both attentional control networks (SN and DAN). Whereas no sex differences were observed, OXT effects on the DN–SN interaction were modulated by autistic traits. Together, the findings suggest that OXT may facilitate efficient attention allocation by modulating the intrinsic functional dynamics between DN components and large-scale networks involved in external attentional demands (SN and DAN).
in Cerebral Cortex Advance Access on December 07, 2018 12:00 AM.
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Different Decision-Making Responses Occupy Different Brain Networks for Information Processing: A Study Based on EEG and TMS

Abstract
This study used large-scale time-varying network analysis to reveal the diverse network patterns during the different decision stages and found that the responses of rejection and acceptance involved different network structures. When participants accept unfair offers, the brain recruits a more bottom-up mechanism with a much stronger information flow from the visual cortex (O2) to the frontal area, but when they reject unfair offers, it displayed a more top-down flow derived from the frontal cortex (Fz) to the parietal and occipital cortices. Furthermore, we performed 2 additional studies to validate the above network models: one was to identify the 2 responses based on the out-degree information of network hub nodes, which results in 70% accuracy, and the other utilized theta burst stimulation (TBS) of transcranial magnetic stimulation (TMS) to modulate the frontal area before the decision-making tasks. We found that the intermittent TBS group demonstrated lower acceptance rates and that the continuous TBS group showed higher acceptance rates compared with the sham group. Similar effects were not observed after TBS of a control site. These results suggest that the revealed decision-making network model can serve as a potential intervention model to alter decision responses.
in Cerebral Cortex Advance Access on December 07, 2018 12:00 AM.
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Early Excitatory Activity-Dependent Maturation of Somatostatin Interneurons in Cortical Layer 2/3 of Mice

Abstract
GABAergic interneurons perform distinct functions during cortical development in the mouse brain. Among the diverse GABAergic neurons present in the brain, early-born somatostatin (SST)-expressing inhibitory interneurons, which are innervated by other interneurons and local pyramidal cells (PCs), act in a neural computational role in circuitry regulation. The synapses between the SST⁺ interneurons and other cells form gradually during development. Here, we traced the developmental course of the electrophysiological properties of SST⁺ interneurons at layer 2/3 of the neocortical secondary motor area (M2) in mouse, and the synaptic connectivity between SST⁺ interneurons and PCs. Also, we used toxin-mediated and genetic method to suppress the activities of PCs, and demonstrate that decreasing excitatory input at early stage (before P1) rather than late stage (after P8) would delay the functional maturation of SST⁺ interneurons. In conclusion, our results indicate that early functional activity of PCs is crucial for the intrinsic maturation of SST⁺ interneurons, following which these interneurons participate in local circuitry.
in Cerebral Cortex Advance Access on December 07, 2018 12:00 AM.
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Temporally Unconstrained Decoding Reveals Consistent but Time-Varying Stages of Stimulus Processing

Abstract
In this article, we propose a method to track trial-specific neural dynamics of stimulus processing and decision making with high temporal precision. By applying this novel method to a perceptual template-matching task, we tracked representational brain states associated with the cascade of neural processing, from early sensory areas to higher order areas that are involved in integration and decision making. We address a major limitation of the traditional decoding approach: that it relies on consistent timing of these processes over trials. Using a TUDA approach, we found that the timing of the cognitive processes involved in perceptual judgments can vary considerably over trials. This revealed that the sequence of processing states was consistent for all subjects and trials, even when the timing of these states varied. Furthermore, we found that the specific timing of states on each trial was related to the quality of performance over trials. Altogether, this work not only highlights the serious pitfalls and misleading interpretations that result from assuming stimulus processing to be synchronous across trials but can also open important avenues to investigate learning and quantify plasticity.
in Cerebral Cortex Advance Access on December 07, 2018 12:00 AM.
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The Role of the Human Auditory Corticostriatal Network in Speech Learning

Abstract
We establish a mechanistic account of how the mature human brain functionally reorganizes to acquire and represent new speech sounds. Native speakers of English learned to categorize Mandarin lexical tone categories produced by multiple talkers using trial-by-trial feedback. We hypothesized that the corticostriatal system is a key intermediary in mediating temporal lobe plasticity and the acquisition of new speech categories in adulthood. We conducted a functional magnetic resonance imaging experiment in which participants underwent a sound-to-category mapping task. Diffusion tensor imaging data were collected, and probabilistic fiber tracking analysis was employed to assay the auditory corticostriatal pathways. Multivariate pattern analysis showed that talker-invariant novel tone category representations emerged in the left superior temporal gyrus (LSTG) within a few hundred training trials. Univariate analysis showed that the putamen, a subregion of the striatum, was sensitive to positive feedback in correctly categorized trials. With learning, functional coupling between the putamen and LSTG increased during error processing. Furthermore, fiber tractography demonstrated robust structural connectivity between the feedback-sensitive striatal regions and the LSTG regions that represent the newly learned tone categories. Our convergent findings highlight a critical role for the auditory corticostriatal circuitry in mediating the acquisition of new speech categories.
in Cerebral Cortex Advance Access on December 07, 2018 12:00 AM.
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Molecular basis for the increased affinity of an RNA recognition motif with re-engineered specificity: A molecular dynamics and enhanced sampling simulations study

by Anna Bochicchio, Miroslav Krepl, Fan Yang, Gabriele Varani, Jiri Sponer, Paolo Carloni
The RNA recognition motif (RRM) is the most common RNA binding domain across eukaryotic proteins. It is therefore of great value to engineer its specificity to target RNAs of arbitrary sequence. This was recently achieved for the RRM in Rbfox protein, where four mutations R118D, E147R, N151S, and E152T were designed to target the precursor to the oncogenic miRNA 21. Here, we used a variety of molecular dynamics-based approaches to predict specific interactions at the binding interface. Overall, we have run approximately 50 microseconds of enhanced sampling and plain molecular dynamics simulations on the engineered complex as well as on the wild-type Rbfox·pre-miRNA 20b from which the mutated systems were designed. Comparison with the available NMR data on the wild type molecules (protein, RNA, and their complex) served to establish the accuracy of the calculations. Free energy calculations suggest that further improvements in affinity and selectivity are achieved by the S151T replacement.
in PLOS Computational Biology: New Articles on December 06, 2018 10:00 PM.
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Function and energy consumption constrain neuronal biophysics in a canonical computation: Coincidence detection

by Michiel W. H. Remme, John Rinzel, Susanne Schreiber
Neural morphology and membrane properties vary greatly between cell types in the nervous system. The computations and local circuit connectivity that neurons support are thought to be the key factors constraining the cells’ biophysical properties. Nevertheless, additional constraints can be expected to further shape neuronal design. Here, we focus on a particularly energy-intense system (as indicated by metabolic markers): principal neurons in the medial superior olive (MSO) nucleus of the auditory brainstem. Based on a modeling approach, we show that a trade-off between the level of performance of a functionally relevant computation and energy consumption predicts optimal ranges for cell morphology and membrane properties. The biophysical parameters appear most strongly constrained by functional needs, while energy use is minimized as long as function can be maintained. The key factors that determine model performance and energy consumption are 1) the saturation of the synaptic conductance input and 2) the temporal resolution of the postsynaptic signals as they reach the soma, which is largely determined by active membrane properties. MSO cells seem to operate close to pareto optimality, i.e., the trade-off boundary between performance and energy consumption that is formed by the set of optimal models. Good performance for drastically lower costs could in theory be achieved by small neurons without dendrites, as seen in the avian auditory system, pointing to additional constraints for mammalian MSO cells, including their circuit connectivity.
in PLOS Computational Biology: New Articles on December 06, 2018 10:00 PM.
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Bayesian adaptive dual control of deep brain stimulation in a computational model of Parkinson’s disease

by Logan L. Grado, Matthew D. Johnson, Theoden I. Netoff
In this paper, we present a novel Bayesian adaptive dual controller (ADC) for autonomously programming deep brain stimulation devices. We evaluated the Bayesian ADC’s performance in the context of reducing beta power in a computational model of Parkinson’s disease, in which it was tasked with finding the set of stimulation parameters which optimally reduced beta power as fast as possible. Here, the Bayesian ADC has dual goals: (a) to minimize beta power by exploiting the best parameters found so far, and (b) to explore the space to find better parameters, thus allowing for better control in the future. The Bayesian ADC is composed of two parts: an inner parameterized feedback stimulator and an outer parameter adjustment loop. The inner loop operates on a short time scale, delivering stimulus based upon the phase and power of the beta oscillation. The outer loop operates on a long time scale, observing the effects of the stimulation parameters and using Bayesian optimization to intelligently select new parameters to minimize the beta power. We show that the Bayesian ADC can efficiently optimize stimulation parameters, and is superior to other optimization algorithms. The Bayesian ADC provides a robust and general framework for tuning stimulation parameters, can be adapted to use any feedback signal, and is applicable across diseases and stimulator designs.
in PLOS Computational Biology: New Articles on December 06, 2018 10:00 PM.
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Activity of Prefrontal Neurons Predict Future Choices during Gambling
Passecker et al. show that specialized neurons in the prelimbic cortex of rats predict the next choice during the outcome evaluation in a gambling task, even for unlikely or uncertain decisions. Disrupting the prelimbic cortex led to excessive risk taking.
in Neuron on December 06, 2018 06:00 PM.
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Expression of RING Finger Protein 38 in Serotonergic Neurons in the Brain of Nile Tilapia, Oreochromis niloticus
Kai Lin Cham, Tomoko Soga, Ishwar S. Parhar
in Frontiers in Neuroanatomy | New and Recent Articles on December 06, 2018 06:00 PM.
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Regional Homogeneity and Multivariate Pattern Analysis of Cervical Spondylosis Neck Pain and the Modulation Effect of Treatment
Jun Chen, Zengjian Wang, Yiheng Tu, Xian Liu, Kristen Jorgenson, Guoxi Ye, Chenlin Lin, Jianhua Liu, Joel Park, Courtney Lang, Bo Liu, Jian Kong
in Frontiers in Neuroscience | Brain Imaging Methods section | New and Recent Articles on December 06, 2018 06:00 PM.
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COORDINATION BETWEEN PREFRONTAL CORTEX CLOCK GENE EXPRESSION AND CORTICOSTERONE CONTRIBUTES TO ENHANCED CONDITIONED FEAR EXTINCTION RECALL
ABSTRACT
PTSD is associated with impaired conditioned fear extinction learning, a ventromedial prefrontal cortex (vmPFC) dependent process. PTSD is also associated with dysregulation of vmPFC, circadian and glucocorticoid hormone function. Rats have rhythmic clock gene expression in the vmPFC that requires appropriate diurnal circulatory patterns of corticosterone (CORT), suggesting the presence of CORT-entrained intrinsic circadian clock function within the PFC. We examined the role of vmPFC clock gene expression and its interaction with CORT profiles in regulation of auditory conditioned fear extinction learning. Extinction learning and recall were examined in male rats trained and tested either in the night (active phase) or in the day (inactive phase). Using a viral vector strategy, Per1 and Per2 clock gene expression were selectively knocked down within the vmPFC. Circulating CORT profiles were manipulated via adrenalectomy (ADX) ± diurnal and acute CORT replacement. Rats trained and tested during the night exhibited superior conditioned fear extinction recall that was absent in rats that had knockdown of vmPFC clock gene expression. Similarly, the superior nighttime extinction recall was absent in ADX rats, but restored in ADX rats given a combination of a diurnal pattern of CORT and acute elevation of CORT during the post-extinction training consolidation period. Thus, conditioned fear extinction learning is regulated in a diurnal fashion that requires normal vmPFC clock gene expression and a combination of circadian and training-associated CORT. Strategic manipulation of these factors may enhance the therapeutic outcome of conditioned fear extinction related treatments in the clinical setting.
SIGNIFICANCE STATEMENT Post Traumatic Stress Disorder is associated with deficits in conditioned fear extinction learning, a prefrontal cortex (PFC)-dependent process, as well as dysregulation of circadian and glucocorticoid hormone function. We examined the role of glucocorticoid-entrained clock gene expression within the PFC on conditioned fear extinction learning, and its interaction with glucocorticoid hormone profiles. We found a prominent time of day difference in extinction recall—superior recall in rats trained and tested at night. This superior recall required normal PFC clock gene expression as well as a combination of a diurnal pattern of circulating glucocorticoids and an acute elevation of glucocorticoids during the extinction learning memory consolidation period. Appropriate alignment of these factors in the clinical setting may enhance extinction learning related outcomes.

in RSS PAP on December 06, 2018 05:45 PM.
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Impaired cognitive function after perineuronal net degradation in the medial prefrontal cortex
Abstract
Perineuronal nets (PNNs) are highly organized components of the extracellular matrix that surround a subset of mature neurons in the central nervous system. These structures play a critical role in regulating neuronal plasticity, particularly during neurodevelopment. Consistent with this role, their presence is associated with functional and structural stability of the neurons they ensheath. A loss of PNNs in the prefrontal cortex has been suggested to contribute to cognitive impairment in disorders such as schizophrenia. However, the direct consequences of PNN loss in medial prefrontal cortex (mPFC) on cognition has not been demonstrated. Here, we examined behavior after disruption of PNNs in mPFC of Long-Evans rats following injection of the enzyme Chondroitinase ABC (ChABC). Our data show that ChABC-treated animals were impaired on tests of object oddity perception. Performance in the cross-modal object recognition task was not significantly different for ChABC-treated rats, although ChABC-treated rats were not able to perform above chance levels whereas control rats were. ChABC treated animals were not significantly different from controls on tests of prepulse inhibition, set-shifting, reversal learning, or tactile and visual object recognition memory. Posthumous immunohistochemistry confirmed significantly reduced PNNs in mPFC due to ChABC treatment. Moreover, PNN density in the mPFC predicted performance on the oddity task, where higher PNN density was associated with better performance. These findings suggest that PNN loss within the mPFC impairs some aspects of object oddity perception and recognition and that PNNs contribute to cognitive function in young adulthood.
Significance Statement Perineuronal nets (PNNs) are organized components of the extracellular matrix that surround mature central nervous system neurons and are critical for the regulation of neuronal plasticity. A loss of PNNs has been observed in schizophrenia and other central nervous system diseases but the exact functional contribution of these structures or the consequences of their loss are not well understood. Here, we show that targeted degradation of PNNs within the medial prefrontal cortex disrupts performance of some tests of object oddity perception and recognition memory. These findings suggest that PNNs and their loss in CNS diseases may contribute directly to the presentation of cognitive dysfunction.

in RSS PAP on December 06, 2018 05:45 PM.
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Sniff invariant odor coding
Abstract
Sampling regulates stimulus intensity and temporal dynamics at the sense organ. Despite variations in sampling behavior, animals must make veridical perceptual judgments about external stimuli. In olfaction, odor sampling varies with respiration, which influences neural responses at the olfactory periphery. Nevertheless, rats were able to perform fine odor intensity judgments despite variations in sniff kinetics. To identify the features of neural activity supporting stable intensity perception, in awake mice we measured responses of Mitral/Tufted (MT) cells to different odors and concentrations across a range of sniff frequencies. Amplitude and latency of the MT cells’ responses vary with sniff duration. A fluid dynamics (FD) model based on odor concentration kinetics in the intranasal cavity can account for this variability. Eliminating sniff waveform dependence of MT cell responses using the FD model allows for significantly better decoding of concentration. This suggests potential schemes for sniff waveform invariant odor concentration coding.
Significance The principles underlying invariant object recognition are of broad interest. The sensory stimuli are subject to external variability, and variability imposed by animal behavior. In olfaction active sampling, sniffing, regulates stimulus intensity and temporal dynamics at the sense organ. Does this interfere with the ability to make accurate perceptual judgments about the physical stimulus? To address this question we initially established that perception of odor intensity is not affected by variations in sampling using behavioral experiments. To identify the features of neural activity that support this invariance in intensity perception, we developed a fluid dynamics model based on odor kinetics in the nose. This model allowed us to find neural representation invariant with respect to sampling thus allowing a stable percept.

in RSS PAP on December 06, 2018 05:45 PM.
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An efficient population density method for modeling neural networks with synaptic dynamics manifesting finite relaxation time and short-term plasticity
Abstract
When incorporating more realistic synaptic dynamics, the computational efficiency of population density methods (PDMs) declines sharply due to the increase in the dimension of master equations. To avoid such a decline, we develop an efficient PDM, termed colored-synapse PDM (csPDM), in which the dimension of the master equations does not depend on the number of synapse-associated state variables in the underlying network model. Our goal is to allow the PDM to incorporate realistic synaptic dynamics that possesses not only finite relaxation time but also short-term plasticity. The model equations of csPDM are derived based on the diffusion approximation on synaptic dynamics and probability density function methods for Langevin equations with colored noise. Numerical examples, given by simulations of the population dynamics of uncoupled exponential integrate-and-fire neurons, show good agreement between the results of csPDM and Monte-Carlo simulations. Compared to the original full-dimensional PDM, the csPDM reveals more excellent computational efficiency because of the lower dimension of the master equations. In addition, it permits network dynamics to possess the short-term plastic characteristics inherited from plastic synapses. The novel csPDM has potential applicability to any spiking neuron models because of no assumptions on neuronal dynamics, and, more importantly, this is the first report of PDM to successfully encompass short-term facilitation/depression properties.
Significance Statement Our study successfully solve an outstanding problem—how to reduce the dimension of population density equations when realistic synaptic dynamics is incorporated. With the newly proposed Fokker-Planck formalism, PDM is conferred STP properties and therefore becomes more widely applicable. As such, our method offers an opportunity to use the PDM to gain new insights into neural mechanisms of brain functions that are strongly dependent on STP synapses. This is the first step toward macroscopic description of large-scale neural network activities, reflected in some commonly used neurophysiological measurements, e.g., EEG, MEG, fMRI and voltage-sensitive dye imaging data.

in RSS PAP on December 06, 2018 05:45 PM.
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Embryonic Neocortical Microglia Express Toll-Like Receptor 9 and Respond to Plasmid DNA Injected into the Ventricle: Technical Considerations Regarding Microglial Distribution in Electroporated Brain Walls
Abstract
Microglia, the resident immune cells in the CNS, play multiple roles during development. In the embryonic cerebral wall, microglia modulate the functions of neural stem/progenitor cells through their distribution in regions undergoing cell proliferation and/or differentiation. Previous studies using CX3CR1-GFP transgenic mice demonstrated that microglia extensively survey these regions. To simultaneously visualize microglia and neural-lineage cells that interact with each other, we applied the in utero electroporation (IUE) technique, which has been widely used for gene-transfer in neurodevelopmental studies, to CX3CR1-GFP mice (males and females). However, we unexpectedly faced a technical problem: although microglia are normally distributed homogeneously throughout the mid-embryonic cortical wall with only limited luminal entry, the intraventricular presence of exogenously derived plasmid DNAs induced microglia to accumulate along the apical surface of the cortex and aggregate in the choroid plexus. This effect was independent of capillary needle puncture of the brain wall or application of electrical pulses. The microglial response occurred at plasmid DNA concentrations lower than those routinely used for IUE, and was mediated by activation of Toll-like receptor 9 (TLR9), an innate immune sensor that recognizes unmethylated cytosine-phosphate guanosine motifs abundant in microbial DNA. Administration of plasmid DNA together with oligonucleotide 2088, the antagonist of TLR9, partially restored the dispersed intramural localization of microglia and significantly decreased luminal accumulation of these cells. Thus, via TLR9, intraventricular plasmid DNA administration causes aberrant distribution of embryonic microglia, suggesting that the behavior of microglia in brain primordia subjected to IUE should be carefully interpreted.

in eNeuro current issue on December 06, 2018 05:30 PM.
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Predicting Progression to Mild Cognitive Impairment

Abstract

Despite much attention to the use of biomarkers for predicting Alzheimer's disease, little information is available at the individual level. We used the population‐based Mayo Clinic Study of Aging to estimate absolute risk of cognitive impairment by biomarker group. Risk increased with age and any biomarker abnormality. For example, a 75‐year‐old with abnormal amyloid and cortical thinning biomarkers has ≈20% chance of cognitive impairment by age 80 whereas with normal biomarkers the chance is <10%. Persons with only one abnormal biomarker had similar intermediate risks.

This article is protected by copyright. All rights reserved.

in Wiley: Annals of Neurology: Table of Contents on December 06, 2018 03:59 PM.
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Challenges of Differential Placebo Effects in Contemporary Medicine: The Example of Brain Stimulation

Abstract

‘Differential placebo effects’ is the concept that different types of placebos (e.g. inert pill versus sham device) may yield different magnitudes of placebo effects. This issue has been pushed into the spotlight by recent clinical trials of new technologies reporting unexpectedly large placebo effects from sham devices/procedures needed to maintain blinding integrity. In this Neurology Grand Rounds, we use transcranial magnetic stimulation as a model to explore the principles and implications of differential placebo effects. We highlight emerging research on the neurobiology of placebo effects and analyze fundamental questions of measuring efficacy in contemporary medicine.

This article is protected by copyright. All rights reserved.

in Wiley: Annals of Neurology: Table of Contents on December 06, 2018 03:58 PM.
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Role of Sensorimotor Cortex in Gestural-Verbal Integration
Dayana Hayek, Agnes Flöel, Daria Antonenko
in Frontiers in Human Neuroscience | New and Recent Articles on December 06, 2018 12:00 PM.
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N-Acetylcysteine Prevents the Spatial Memory Deficits and the Redox-Dependent RyR2 Decrease Displayed by an Alzheimer’s Disease Rat Model
Jamileth More, Nadia Galusso, Pablo Veloso, Luis Montecinos, José Pablo Finkelstein, Gina Sanchez, Ricardo Bull, José Luis Valdés, Cecilia Hidalgo, Andrea Paula-Lima
in Frontiers in Aging Neuroscience | New and Recent Articles on December 06, 2018 12:00 PM.
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Volumetric MRI Analysis of a Case of Severe Ventriculomegaly
Gésine L. Alders, Luciano Minuzzi, Sachin Sarin, Benicio N. Frey, Geoffrey B. Hall, Zainab Samaan
in Frontiers in Human Neuroscience | New and Recent Articles on December 06, 2018 06:00 AM.
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Investigating Multiple Streams of Consciousness: Using Descriptive Experience Sampling to Explore Internally and Externally Directed Streams of Thought
Charles Fernyhough, Ben Alderson-Day, Russell T. Hurlburt, Simone Kühn
in Frontiers in Human Neuroscience | New and Recent Articles on December 06, 2018 06:00 AM.
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Brain Mechanisms Underlying Visuo-Orthographic Deficits in Children With Developmental Dyslexia
Fan Cao, Xin Yan, Gregory J. Spray, Yanni Liu, Yuan Deng
in Frontiers in Human Neuroscience | New and Recent Articles on December 06, 2018 06:00 AM.
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Age-Related Alterations in Electroencephalography Connectivity and Network Topology During n-Back Working Memory Task
Fengzhen Hou, Cong Liu, Zhinan Yu, Xiaodong Xu, Junying Zhang, Chung-Kang Peng, Chunyong Wu, Albert Yang
in Frontiers in Human Neuroscience | New and Recent Articles on December 06, 2018 06:00 AM.
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The Emerging Role of Mechanics in Synapse Formation and Plasticity
Devrim Kilinc
in Frontiers in Cellular Neuroscience | New and Recent Articles on December 06, 2018 06:00 AM.
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In vivo Optogenetic Approach to Study Neuron-Oligodendroglia Interactions in Mouse Pups
Domiziana Ortolani, Blandine Manot-Saillet, David Orduz, Fernando C. Ortiz, Maria Cecilia Angulo
in Frontiers in Cellular Neuroscience | New and Recent Articles on December 06, 2018 06:00 AM.
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Amnestic Mild Cognitive Impairment Is Associated With Frequency-Specific Brain Network Alterations in Temporal Poles
Francesca Jacini, Pierpaolo Sorrentino, Anna Lardone, Rosaria Rucco, Fabio Baselice, Carlo Cavaliere, Marco Aiello, Mario Orsini, Alessandro Iavarone, Valentino Manzo, Anna Carotenuto, Carmine Granata, Arjan Hillebrand, Giuseppe Sorrentino
in Frontiers in Aging Neuroscience | New and Recent Articles on December 06, 2018 06:00 AM.
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Effects of Phase-Locking Deficits on Speech Recognition in Older Adults With Presbycusis
Wenyang Hao, Qian Wang, Liang Li, Yufei Qiao, Zhiqiang Gao, Daofeng Ni, Yingying Shang
in Frontiers in Aging Neuroscience | New and Recent Articles on December 06, 2018 06:00 AM.
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Endocytic Adaptor Protein HIP1R Controls Intracellular Trafficking of Epidermal Growth Factor Receptor in Neuronal Dendritic Development
Qian Yang, Lin Peng, Yu Wu, Yanan Li, Ling Wang, Jian-hong Luo, Junyu Xu
in Frontiers in Molecular Neuroscience | New and Recent Articles on December 06, 2018 06:00 AM.
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Altered Default Mode and Sensorimotor Network Connectivity With Striatal Subregions in Primary Insomnia: A Resting-State Multi-Band fMRI Study
Li Wang, Kun Wang, Jiang-Hong Liu, Yu-Ping Wang
in Frontiers in Neuroscience | Brain Imaging Methods section | New and Recent Articles on December 06, 2018 06:00 AM.
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A Comparative Atlas-Based Recognition of Mild Cognitive Impairment With Voxel-Based Morphometry
Zhuqing Long, Jinchang Huang, Bo Li, Zuojia Li, Zihao Li, Hongwen Chen, Bin Jing
in Frontiers in Neuroscience | Brain Imaging Methods section | New and Recent Articles on December 06, 2018 06:00 AM.
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Tideglusib Rescues Neurite Pathology of SPG11 iPSC Derived Cortical Neurons
Tatyana Pozner, Annika Schray, Martin Regensburger, Dieter Chichung Lie, Ursula Schlötzer-Schrehardt, Jürgen Winkler, Soeren Turan, Beate Winner
in Frontiers in Neuroscience | Neurogenesis section | New and Recent Articles on December 06, 2018 06:00 AM.
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A Novel Approach for Modeling Neural Responses to Joint Perturbations Using the NARMAX Method and a Hierarchical Neural Network
Runfeng Tian, Yuan Yang, Frans C. T. van der Helm, Julius P. A. Dewald
in Frontiers in Computational Neuroscience | New and Recent Articles on December 06, 2018 06:00 AM.
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Isotropic 25-Micron 3D Neuroimaging Using ex vivo Microstructural Manganese-Enhanced MRI (MEMRI)
Chika Sato, Kazuhiko Sawada, David Wright, Tatsuya Higashi, Ichio Aoki
in Frontiers in Neural Circuits | New and Recent Articles on December 06, 2018 06:00 AM.
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Neural Progenitor Cell Terminology
Verónica Martínez-Cerdeño, Stephen C. Noctor
in Frontiers in Neuroanatomy | New and Recent Articles on December 06, 2018 06:00 AM.
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Optimal models of decision-making in dynamic environments. (arXiv:1812.01727v1 [q-bio.NC])

Nature is in constant flux, so animals must account for changes in their environment when making decisions. How animals learn the timescale of such changes and adapt their decision strategies accordingly is not well understood. Recent psychophysical experiments have shown humans and other animals can achieve near-optimal performance at two alternative forced choice (2AFC) tasks in dynamically changing environments. Characterization of performance requires the derivation and analysis of computational models of optimal decision-making policies on such tasks. We review recent theoretical work in this area, and discuss how models compare with subjects' behavior in tasks where the correct choice or evidence quality changes in dynamic, but predictable, ways.

in q-bio.NC updates on arXiv.org on December 06, 2018 01:30 AM.
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When remembering is rewarding

When remembering is rewarding
When remembering is rewarding, Published online: 06 December 2018; doi:10.1038/s41583-018-0110-4
In mice, long-term potentiation of hippocampal–nucleus accumbens synapses is required for the formation of reward-related memories.
in Nature Reviews Neuroscience - Issue - nature.com science feeds on December 06, 2018 12:00 AM.
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Cell-type-specific programs for activity-regulated gene expression

Publication date: June 2019
Source: Current Opinion in Neurobiology, Volume 56
Author(s): Jesse M Gray, Ivo Spiegel
Experience leaves a lasting mark on neural circuit function in part through activity-regulated gene (ARG) expression. New genome wide approaches have revealed that ARG programs are highly cell-type-specific, raising the possibility that they mediate different forms of experience-dependent plasticity in different cell types. The cell-type specificity of these gene programs is achieved by a combination of cell-intrinsic mechanisms that determine the transcriptional response of each neuronal subtype to a given stimulus and by cell-extrinsic mechanisms that influence the nature of the stimulus a cell receives. A better understanding of these mechanisms could usher in an era of molecular systems neuroscience in which genetic perturbations of cell-type-specific plasticities are assessed using electrophysiology and in vivo imaging to reveal the neural basis of adaptive behaviors.

in ScienceDirect Publication: Current Opinion in Neurobiology on December 05, 2018 06:00 PM.
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This Week in The Journal

in Journal of Neuroscience current issue on December 05, 2018 05:30 PM.
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Neural Evidences of Hierarchical Cognitive Control during Haptic Processing: An fMRI Study
Abstract
Interacting with our immediate surroundings requires constant manipulation of objects. Dexterous manipulation depends on comparison between actual and predicted sensory input, with these predictions calculated by means of lower- and higher-order corollary discharge signals. However, there is still scarce knowledge about the hierarchy in the neural architecture supporting haptic monitoring during manipulation. The present study aimed to assess this issue focusing on the cross talk between lower-order sensory and higher-order associative regions. We used functional magnetic resonance imaging in humans during a haptic discrimination task in which participants had to judge whether a touched shape or texture corresponded to an expected stimulus whose name was previously presented. Specialized haptic regions identified with an independent localizer task did not differ between expected and unexpected conditions, suggesting their lack of involvement in tactile monitoring. When presented stimuli did not match previous expectations, the left supramarginal gyrus (SMG), middle temporal, and medial prefrontal cortices were activated regardless of the nature of the haptic mismatch (shape/texture). The left primary somatosensory area (SI) responded differently to unexpected shapes and textures in line with a specialized detection of haptic mismatch. Importantly, connectivity analyses revealed that the left SMG and SI were more functionally coupled during unexpected trials, emphasizing their interaction. The results point for the first time to a hierarchical organization in the neural substrates underlying haptic monitoring during manipulation with the SMG as a higher-order hub comparing actual and predicted somatosensory input, and SI as a lower-order site involved in the detection of more specialized haptic mismatch.

in eNeuro current issue on December 05, 2018 05:30 PM.
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Altered Sensory Insular Connectivity in Chronic Postsurgical Pain Patients
Yin Ying Ching, Chenhao Wang, Terence Tay, Yng Miin Loke, Phua Hwee Tang, Ban Leong Sng, Juan Zhou
in Frontiers in Human Neuroscience | New and Recent Articles on December 05, 2018 12:00 PM.
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Cognitive Control Over Visual Motion Processing – Are Children With ADHD Especially Compromised? A Pilot Study of Flanker Task Event-Related Potentials
Bettina Lange-Malecki, Stefan Treue, Aribert Rothenberger, Björn Albrecht
in Frontiers in Human Neuroscience | New and Recent Articles on December 05, 2018 06:00 AM.
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Editorial: The Contribution of Postural Adjustments to Body Balance and Motor Performance
Eric Yiou, Alain Hamaoui, Gilles Allali
in Frontiers in Human Neuroscience | New and Recent Articles on December 05, 2018 06:00 AM.
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Retinoic Acid Regulates Endothelial β-catenin Expression and Pericyte Numbers in the Developing Brain Vasculature
Stephanie Bonney, Brenna J. C. Dennison, Megan Wendlandt, Julie A. Siegenthaler
in Frontiers in Cellular Neuroscience | New and Recent Articles on December 05, 2018 06:00 AM.
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Kinase-Based Taming of Brain Microglia Toward Disease-Modifying Therapy
Sun-Hwa Lee, Kyoungho Suk
in Frontiers in Cellular Neuroscience | New and Recent Articles on December 05, 2018 06:00 AM.
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Disorders of Body Weight, Sleep and Circadian Rhythm as Manifestations of Hypothalamic Dysfunction in Alzheimer’s Disease
Abigail J. Hiller, Makoto Ishii
in Frontiers in Cellular Neuroscience | New and Recent Articles on December 05, 2018 06:00 AM.
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Photolysis of a Caged, Fast-Equilibrating Glutamate Receptor Antagonist, MNI-Caged γ-D-Glutamyl-Glycine, to Investigate Transmitter Dynamics and Receptor Properties at Glutamatergic Synapses
Francisco Palma-Cerda, George Papageorgiou, Boris Barbour, Céline Auger, David Ogden
in Frontiers in Cellular Neuroscience | New and Recent Articles on December 05, 2018 06:00 AM.
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Mechanisms of AMPA Receptor Endosomal Sorting
Gabrielle T. Parkinson, Jonathan G. Hanley
in Frontiers in Molecular Neuroscience | New and Recent Articles on December 05, 2018 06:00 AM.
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Do We Need a Human post mortem Whole-Brain Anatomical Ground Truth in in vivo Magnetic Resonance Imaging?
Anneke Alkemade, Josephine M. Groot, Birte U. Forstmann
in Frontiers in Neuroanatomy | New and Recent Articles on December 05, 2018 06:00 AM.
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Three-Dimensional Nanostructure of an Intact Microglia Cell
Giulia Bolasco, Laetitia Weinhard, Tom Boissonnet, Ralph Neujahr, Cornelius T. Gross
in Frontiers in Neuroanatomy | New and Recent Articles on December 05, 2018 06:00 AM.
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A Tight Upper Bound on Mutual Information. (arXiv:1812.01475v1 [cs.IT])

We derive a tight lower bound on equivocation (conditional entropy), or equivalently a tight upper bound on mutual information between a signal variable and channel outputs. The bound is in terms of the joint distribution of the signals and maximum a posteriori decodes (most probable signals given channel output). As part of our derivation, we describe the key properties of the distribution of signals, channel outputs and decodes, that minimizes equivocation and maximizes mutual information. This work addresses a problem in data analysis, where mutual information between signals and decodes is sometimes used to lower bound the mutual information between signals and channel outputs. Our result provides a corresponding upper bound.

in q-bio.NC updates on arXiv.org on December 05, 2018 01:30 AM.
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The Shift in brain-state induced by tDCS: an EEG study. (arXiv:1812.01342v1 [q-bio.NC])

Transcranial direct current stimulation (tDCS) is known to have a modulatory effect on neural tissue and that it is polarity specific. It is also shown that tDCS demonstrated the lasting effect in therapeutic applications. The main aim of the study was to examine the effects of tDCS on cortical dynamics by analyzing EEG recordings. We applied here measures taken from Recurrence Quantification Analysis, Mean State Shift (MSS) and State Variance (SV) which were previously used to detect changes in brain-state dynamics after TMS. The studied cohort comprised of 16 healthy subjects; all subjects received anodal and cathodal tDCS, which were given in two separate sessions on the same day. The EEG was recorded from 10 electrodes, positioned over left motor cortex and mirroring right cortex corresponding to 10/20 standard. From three traces of recordings (pre, post1 and post2/before the stimulation, immediately after and 30min after tDCS) we extracted five different intervals (T1-T5) comprising of 500 samples. After calculating MSS and SV on those epochs and statistical testing for a significant difference, we applied Principal Component Analysis (PCA) on the same time series to check whether the data are separable. The results show that tDCS exert polarity specific effects on the MSS as shown by significantly lower MSS values after cathodal stimulation compared to anodal stimulation. Cathodal stimulation affected the SV, as compared to anodal stimulation, which did not lead to detectable changes. We are offering here for the first time an informative PCA visualization of a time-effect of a tDCS stimulation on brain state shift. Further research is needed to elucidate for how long that change can be detected and what neurobiological changes are introduced by that phenomena.

in q-bio.NC updates on arXiv.org on December 05, 2018 01:30 AM.
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Restoring walking

Restoring walking
Restoring walking, Published online: 05 December 2018; doi:10.1038/s41583-018-0109-x
A study shows that application of spatiotemporally patterned epidural electrical stimulation alongside rehabilitation allowed individuals with spinal cord injury and severe locomotor deficits to walk with limited assistance.
in Nature Reviews Neuroscience - Issue - nature.com science feeds on December 05, 2018 12:00 AM.
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To sleep, to remember

To sleep, to remember
To sleep, to remember, Published online: 05 December 2018; doi:10.1038/s41583-018-0108-y
To sleep, to remember
in Nature Reviews Neuroscience - Issue - nature.com science feeds on December 05, 2018 12:00 AM.
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Closing the loop

Closing the loop
Closing the loop, Published online: 05 December 2018; doi:10.1038/s41583-018-0107-z
Closing the loop
in Nature Reviews Neuroscience - Issue - nature.com science feeds on December 05, 2018 12:00 AM.
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Patchwork subiculum

Patchwork subiculum
Patchwork subiculum, Published online: 05 December 2018; doi:10.1038/s41583-018-0106-0
Patchwork subiculum
in Nature Reviews Neuroscience - Issue - nature.com science feeds on December 05, 2018 12:00 AM.
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Gone FISHing

Gone FISHing
Gone FISHing, Published online: 05 December 2018; doi:10.1038/s41583-018-0105-1
Gone FISHing
in Nature Reviews Neuroscience - Issue - nature.com science feeds on December 05, 2018 12:00 AM.
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Food intake — feeling the heat

Food intake — feeling the heat
Food intake — feeling the heat, Published online: 05 December 2018; doi:10.1038/s41583-018-0104-2
Meal-associated thermogenesis in brown fat is triggered by the gut hormone secretin and signals to the brain to promote satiation in mice.
in Nature Reviews Neuroscience - Issue - nature.com science feeds on December 05, 2018 12:00 AM.
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Non-nociceptive roles of opioids in the CNS: opioids’ effects on neurogenesis, learning, memory and affect

Non-nociceptive roles of opioids in the CNS: opioids’ effects on neurogenesis, learning, memory and affect
Non-nociceptive roles of opioids in the CNS: opioids’ effects on neurogenesis, learning, memory and affect, Published online: 05 December 2018; doi:10.1038/s41583-018-0092-2
Maladaptive modulation of learning, memory and affect by opioids is linked to dysfunctional neurogenesis. In this Review, Kibaly and colleagues discuss this link and how strategies that target neurogenesis to rescue opioid-dependent learning, memory and affect impairments constitute future directions for anti-addiction therapies.
in Nature Reviews Neuroscience - Issue - nature.com science feeds on December 05, 2018 12:00 AM.
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An Unbiased View of Neural Networks: More than Meets the Eye
In this issue of Neuron, Macé et al. (2018) use whole-brain functional ultrasound imaging in mice to unveil the circuits involved reflexive eye movements. They separated the sensory and motor networks and discovered that certain eye movements robustly suppress the amygdala.
in Neuron on December 05, 2018 12:00 AM.
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Conducting the Neural Symphony of Memory Replay
Hippocampal sharp-wave ripple oscillations and sequence replay events are important for memory. Ramirez-Villegas et al. present a model that dissects cellular mechanisms of SWR generation in the CA3-CA1 circuit, and explains the network features of slow-gamma coordination and sequence replay.
in Neuron on December 05, 2018 12:00 AM.
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CHD2: One Gene, Many Roles
Mutations in the chromodomain helicase DNA-binding 2 (CHD2) gene have been found in patients with a range of neurodevelopmental disorders. In this issue of Neuron, Kim et al. (2018) showed that Chd2 haploinsufficiency compromises cortical development, synaptic function, and memory in mice.
in Neuron on December 05, 2018 12:00 AM.
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A Path(way) to Keeping Your Synapses on an Even Keel
In this issue of Neuron, Harris et al. (2018) show that a signal transduction pathway normally exploited by the innate immune system in recognizing foreign agents plays a critical role in controlling a synapse’s ability to maintain stability in the efficacy of synaptic transmission over both rapid and prolonged timescales.
in Neuron on December 05, 2018 12:00 AM.
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Whole-Brain Functional Ultrasound Imaging Reveals Brain Modules for Visuomotor Integration
Macé et al. developed an approach for imaging whole-brain activity during mouse behavior using ultrasound. They revealed many brain regions activated during the optokinetic reflex, a visuomotor behavior that stabilizes gaze. They parsed them into functional modules using reflex perturbations.
in Neuron on December 05, 2018 12:00 AM.
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Astrocytes “Chordinate” Synapse Maturation and Plasticity
A key step in excitatory synapse maturation is the switch in AMPA receptor subunit composition to GluA2-containing calcium-impermeable receptors. Now, Blanco-Suarez et al. (2018) demonstrate that astrocyte-secreted chordin-like 1 drives this process, enabling synapse maturation and limiting plasticity.
in Neuron on December 05, 2018 12:00 AM.
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Physiological Models of Human Neuronal Development and Disease
Human neural network development occurs at stages inaccessible to longitudinal monitoring. By transplanting human neurons to the adult mouse brain, recent studies explore human neural circuit formation in realistic cellular and physiological environments, establishing new models for human neurodevelopmental disorders.
in Neuron on December 05, 2018 12:00 AM.
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Neuronal Polarization Packs a One-Two Punch
In this issue of Neuron, Ambrozkiewicz et al. (2018) define a new molecular circuit controlling neuronal polarization and migration through the transcription factor SOX9 to coordinate the production of regulators of both protein synthesis and degradation.
in Neuron on December 05, 2018 12:00 AM.
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Hierarchical Predictive Information Is Channeled by Asymmetric Oscillatory Activity
Predictive coding and neural oscillations are two descriptive levels of brain functioning whose overlap is not yet understood. Chao et al. (2018) now show that hierarchical predictive coding is instantiated by asymmetric information channeling in the γ and α/β oscillatory ranges.
in Neuron on December 05, 2018 12:00 AM.
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Cracking the Function of Layers in the Sensory Cortex
In this perspective, Adesnik and Naka outline the road map to overcome the existing conceptual and technical challenges for obtaining a detailed understanding of the role of cortical layers in sensory computation and perception.
in Neuron on December 05, 2018 12:00 AM.
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Yoga Practitioners Uniquely Activate the Superior Parietal Lobule and Supramarginal Gyrus During Emotion Regulation
Katie P. Wadden, Nicholas J. Snow, Peder Sande, Sian Slawson, Tom Waller, Lara A. Boyd
in Frontiers in Integrative Neuroscience | New and Recent Articles on December 04, 2018 06:00 PM.
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Development of GABAergic Inputs Is Not Altered in Early Maturation of Adult Born Dentate Granule Neurons in Fragile X Mice
Abstract
Fragile X syndrome (FXS) is the most common form of inherited mental retardation and the most common known cause of autism. Loss of fragile X mental retardation protein (FMRP) in mice (Fmr1 KO) leads to altered synaptic and circuit maturation in the hippocampus that is correlated with alterations in hippocampal-dependent behaviors. Previous studies have demonstrated that loss of FMRP increased the rate of proliferation of progenitor cells and altered their fate specification in adult Fmr1 KO mice. While these studies clearly demonstrate a role for FMRP in adult neurogenesis in the hippocampus, it is not known whether the functional synaptic maturation and integration of adult-born dentate granule cells (abDGCs) into hippocampal circuits is affected in Fmr1 KO mice. Here, we used retroviral labeling to birthdate abDGCs in Fmr1 KO mice which allowed us to perform targeted patch clamp recording to measure the development of synaptic inputs to these neurons at precise time points after differentiation. The frequency and amplitude of spontaneous GABAergic events increased over the first three weeks after differentiation; however, this normal development of GABAergic synapses was not altered in Fmr1 KO mice. Furthermore, the relatively depolarized GABA reversal potential (E_GABA) in immature abDGCs was unaffected by loss of FMRP as was the development of dendritic arbor of the adult generated neurons. These studies systematically characterized the functional development of abDGCs during the first four weeks after differentiation and demonstrate that the maturation of GABAergic synaptic inputs to these neurons is not grossly affected by the loss of FMRP.

in eNeuro current issue on December 04, 2018 05:38 PM.
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Heavy Alcohol Exposure Activates Astroglial Hemichannels and Pannexons in the Hippocampus of Adolescent Rats: Effects on Neuroinflammation and Astrocyte Arborization
Gonzalo I. Gómez, Romina V. Falcon, Carola J. Maturana, Valeria C. Labra, Nicole Salgado, Consuelo A. Rojas, Juan E. Oyarzun, Waldo Cerpa, Rodrigo A. Quintanilla, Juan A. Orellana
in Frontiers in Cellular Neuroscience | New and Recent Articles on December 04, 2018 12:00 PM.
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Spinal Afferent Innervation of the Colon and Rectum
Stuart M. Brierley, Timothy J. Hibberd, Nick J. Spencer
in Frontiers in Cellular Neuroscience | New and Recent Articles on December 04, 2018 12:00 PM.
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Effects of Aging on Postural Responses to Visual Perturbations During Fast Pointing
Yajie Zhang, Eli Brenner, Jacques Duysens, Sabine Verschueren, Jeroen B. J. Smeets
in Frontiers in Aging Neuroscience | New and Recent Articles on December 04, 2018 12:00 PM.
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An Investigation Into Physical Frailty as a Link Between the Gut Microbiome and Cognitive Health
Serena Verdi, Matthew A. Jackson, Michelle Beaumont, Ruth C. E. Bowyer, Jordana T. Bell, Tim D. Spector, Claire J. Steves
in Frontiers in Aging Neuroscience | New and Recent Articles on December 04, 2018 12:00 PM.
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Protective Effect of Hydrogen on Sodium Iodate-Induced Age-Related Macular Degeneration in Mice
Yanli Liu, Ruichan Li, Jing Xie, Jiehua Hu, Xudong Huang, Fu Ren, Lihua Li
in Frontiers in Aging Neuroscience | New and Recent Articles on December 04, 2018 12:00 PM.
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Catecholamines in Post-traumatic Stress Disorder: A Systematic Review and Meta-Analysis
Xiongfeng Pan, Atipatsa C. Kaminga, Shi Wu Wen, Aizhong Liu
in Frontiers in Molecular Neuroscience | New and Recent Articles on December 04, 2018 12:00 PM.
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UBE3A and Its Link With Autism
Naman Vatsa, Nihar Ranjan Jana
in Frontiers in Molecular Neuroscience | New and Recent Articles on December 04, 2018 12:00 PM.
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CaMKII Isoforms in Learning and Memory: Localization and Function
Gisela Zalcman, Noel Federman, Arturo Romano
in Frontiers in Molecular Neuroscience | New and Recent Articles on December 04, 2018 12:00 PM.
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Discordant Responses to MAPK Pathway Stimulation Include Axonal Growths in Adult Drosophila Photoreceptors
Kirk L. Mecklenburg, Forrest P. Weghorst, Stephanie A. Freed, Joseph E. O’Tousa
in Frontiers in Molecular Neuroscience | New and Recent Articles on December 04, 2018 12:00 PM.
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Ca2+ Requirements for Long-Term Depression Are Frequency Sensitive in Purkinje Cells
C. G. Zamora Chimal, Erik De Schutter
in Frontiers in Molecular Neuroscience | New and Recent Articles on December 04, 2018 12:00 PM.
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Synaptic Functions of Hemichannels and Pannexons: A Double-Edged Sword
Verónica Abudara, Mauricio A. Retamal, Rodrigo Del Rio, Juan A. Orellana
in Frontiers in Molecular Neuroscience | New and Recent Articles on December 04, 2018 12:00 PM.
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Formalizing the Function of Anterior Insula in Rapid Adaptation
Peter Bossaerts
in Frontiers in Integrative Neuroscience | New and Recent Articles on December 04, 2018 12:00 PM.
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Cost-Effectiveness of Tele-Video-Consultation for the Neuro-Surgical Emergency Management at the General Hospitals in Italy
Rajendra Kadel, Sara Evans-Lacko, Andrea Tramarin, Giampaolo Stopazzolo
in Frontiers in Neuroscience | Neural Technology section | New and Recent Articles on December 04, 2018 12:00 PM.
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Editorial: Adult Neurogenesis: Beyond Rats and Mice
Luca Bonfanti, Irmgard Amrein
in Frontiers in Neuroscience | Neurogenesis section | New and Recent Articles on December 04, 2018 12:00 PM.
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Aceruloplasminemia: Waiting for an Efficient Therapy
Alberto Piperno, Massimo Alessio
in Frontiers in Neuroscience | Neurodegeneration section | New and Recent Articles on December 04, 2018 12:00 PM.
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Disruption in Brain Phospholipid Content in a Humanized Tau Transgenic Model Following Repetitive Mild Traumatic Brain Injury
Joseph O. Ojo, Moustafa Algamal, Paige Leary, Laila Abdullah, Benoit Mouzon, James E. Evans, Michael Mullan, Fiona Crawford
in Frontiers in Neuroscience | Neurodegeneration section | New and Recent Articles on December 04, 2018 12:00 PM.
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Ion Beam Assisted E-Beam Deposited TiN Microelectrodes—Applied to Neuronal Cell Culture Medium Evaluation
Tomi Ryynänen, Maria Toivanen, Turkka Salminen, Laura Ylä-Outinen, Susanna Narkilahti, Jukka Lekkala
in Frontiers in Neuroscience | Neural Technology section | New and Recent Articles on December 04, 2018 12:00 PM.
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Cross-Regional Gradient of Dendritic Morphology in Isochronically-Sourced Mouse Supragranular Pyramidal Neurons
Zachary Logan Holley, Katherine M. Bland, Zachary O. Casey, Christopher J. Handwerk, George S. Vidal
in Frontiers in Neuroanatomy | New and Recent Articles on December 04, 2018 12:00 PM.
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Fractionating Blunted Reward Processing Characteristic of Anhedonia by Over-Activating Primate Subgenual Anterior Cingulate Cortex
Using intracerebral microinfusions in marmosets, Alexander et al. demonstrate a causal role for sgACC/25 over-activity in specific aspects of impaired reward processing associated with anhedonia. Ketamine successfully ameliorates related impairments by modulating activity within a dysfunctional neural circuit involved in reward processing and interoception.
in Neuron on December 04, 2018 12:00 AM.
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Single-Neuron Correlates of Error Monitoring and Post-Error Adjustments in Human Medial Frontal Cortex
Fu et al. identify single-neuron correlates of error self-monitoring in the human medial frontal cortex. Error neurons respond first in pre-SMA, followed by dACC. The activity of error neurons predicts the amplitude of the error-related negativity trial by trial.
in Neuron on December 04, 2018 12:00 AM.
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Predictive models avoid excessive reductionism in cognitive neuroimaging

Publication date: April 2019
Source: Current Opinion in Neurobiology, Volume 55
Author(s): Gaël Varoquaux, Russell A Poldrack
Understanding the organization of complex behavior as it relates to the brain requires modeling the behavior, the relevant mental processes, and the corresponding neural activity. Experiments in cognitive neuroscience typically study a psychological process via controlled manipulations, reducing behavior to one of its components. Such reductionism can easily lead to paradigm-bound theories. Predictive models can generalize brain-mind associations to arbitrary new tasks and stimuli. We argue that they are needed to broaden theories beyond specific paradigms. Predicting behavior from neural activity can support robust reverse inference, isolating brain structures that support particular mental processes. The converse prediction enables modeling brain responses as a function of a complete description of the task, rather than building on oppositions.

in ScienceDirect Publication: Current Opinion in Neurobiology on December 03, 2018 06:00 PM.
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Müller Cell Regulated Microglial Activation and Migration in Rats With N-Methyl-N-Nitrosourea-Induced Retinal Degeneration
Shuai Zhang, Shanshan Zhang, Wenqing Gong, Guopei Zhu, Songtao Wang, Yalin Wang, Michael Halim, Kaidi Wang, Guomin Zhou, Qiong Liu
in Frontiers in Neuroscience | Neurodegeneration section | New and Recent Articles on December 03, 2018 06:00 PM.
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Spinal cord injury in rats disrupts the circadian system
Abstract
Spinal cord injury (SCI) perturbs many physiological systems. The circadian system helps maintain homeostasis throughout the body by synchronizing physiological and behavioural functions to predictable daily events. Whether disruption of these coordinated daily rhythms contributes to SCI-associated pathology remains under-studied. Here, we hypothesized that SCI in rats would dysregulate several prominent circadian outputs including glucocorticoids, core temperature, activity, neuroinflammation, and circadian gene networks. Female and male Sprague-Dawley rats were subjected to clinically relevant thoracic (T-) 9 moderate contusion SCI (or laminectomy sham surgery). Diurnal measures – including rhythms of plasma corticosterone (CORT), body temperature and activity (using small implanted transmitters), and intraspinal circadian and inflammatory gene expression – were studied prior to and post-surgery. SCI caused overall increases and disrupted rhythms of the major rodent glucocorticoid, CORT. Pre-surgery and sham rats displayed expected rhythms in body temperature and activity, whereas rats with SCI had blunted daily rhythms in body temperature and activity. In parallel, SCI disrupted intraspinal rhythms of circadian clock gene expression. Circadian clock genes can act as transcriptional regulators of inflammatory pathways. Indeed, SCI rats also showed dysregulated rhythms in inflammatory gene expression in both the epicenter and distal spinal cord. Our data show that moderate SCI in rats causes wide-ranging diurnal rhythm dysfunction, which is severe at acute time points, and gradually recovers over time. Normalizing post-SCI diurnal rhythms could enhance recovery of homeostasis and quality-of-life.
Significance Statement Spinal cord injury (SCI) can cause physiologic dysfunction throughout the body. Internal physiologic function is typically synchronized with the environment through the circadian system. Despite the crucial roles of the spinal cord and the circadian system in optimizing whole-body function, it remains unclear whether SCI alters diurnal rhythms. Here, we hypothesized that SCI would disrupt key circadian output and feedback mechanisms. Moderate SCI in rats caused widespread disruption of diurnal measures – including glucocorticoids, body temperature, locomotor activity, and intraspinal clock and inflammatory gene expression. We identify the circadian system as a novel potential target for SCI therapies.

in RSS PAP on December 03, 2018 05:32 PM.
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Oscillations in Spontaneous and Visually Evoked Neuronal Activity in the Superficial Layers of the Cat's Superior Colliculus
Andrzej T. Foik, Anaida Ghazaryan, Wioletta J. Waleszczyk
in Frontiers in Systems Neuroscience | New and Recent Articles on December 03, 2018 12:00 PM.
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Cochlear Synaptopathy Changes Sound-Evoked Activity Without Changing Spontaneous Discharge in the Mouse Inferior Colliculus
Luke A. Shaheen, M. Charles Liberman
in Frontiers in Systems Neuroscience | New and Recent Articles on December 03, 2018 06:00 AM.
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A Ketogenic Diet Improves Cognition and Has Biochemical Effects in Prefrontal Cortex That Are Dissociable From Hippocampus
Abbi R. Hernandez, Caesar M. Hernandez, Keila Campos, Leah Truckenbrod, Quinten Federico, Brianna Moon, Joseph A. McQuail, Andrew P. Maurer, Jennifer L. Bizon, Sara N. Burke
in Frontiers in Aging Neuroscience | New and Recent Articles on December 03, 2018 06:00 AM.
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Differential pH Dynamics in Synaptic Vesicles From Intact Glutamatergic and GABAergic Synapses
Melissa A. Herman, Thorsten Trimbuch, Christian Rosenmund
in Frontiers in Synaptic Neuroscience | New and Recent Articles on December 03, 2018 06:00 AM.
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Tau’s Three-Repeat Domain and EFhd2 Co-incubation Leads to Increased Thioflavin Signal
Irving E. Vega, Alexandra Sutter, Luke Parks, Andrew Umstead, Magdalena I. Ivanova
in Frontiers in Neuroscience | Neurodegeneration section | New and Recent Articles on December 03, 2018 06:00 AM.
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A Real-Time Phase-Locking System for Non-invasive Brain Stimulation
Farrokh Mansouri, Peter Fettes, Laura Schulze, Peter Giacobbe, Jose Zariffa, Jonathan Downar
in Frontiers in Neuroscience | Neural Technology section | New and Recent Articles on December 03, 2018 06:00 AM.
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Rapamycin Enhances Mitophagy and Attenuates Apoptosis After Spinal Ischemia-Reperfusion Injury
Qiang Li, Shane Gao, Zhanrong Kang, Meiyan Zhang, Xin Zhao, Yu Zhai, Jianming Huang, Guo-Yuan Yang, Wanju Sun, Jian Wang
in Frontiers in Neuroscience | Neurodegeneration section | New and Recent Articles on December 03, 2018 06:00 AM.
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Complex Dynamics in Simplified Neuronal Models: Reproducing Golgi Cell Electroresponsiveness
Alice Geminiani, Claudia Casellato, Francesca Locatelli, Francesca Prestori, Alessandra Pedrocchi, Egidio D'Angelo
in Frontiers in Neuroinformatics | New and Recent Articles on December 03, 2018 06:00 AM.
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How the Internally Organized Direction Sense Is Used to Navigate
Park et al. show that medial entorhinal cortex head-direction cell discharge is internally organized but registers inconsistently and temporarily to external landmarks during navigation, indicating the navigation system operates unlike a GPS but like variably oriented etak systems without a global reference.
in Neuron on December 03, 2018 12:00 AM.
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Mechanisms Underlying Microbial-Mediated Changes in Social Behavior in Mouse Models of Autism Spectrum Disorder
Precision microbial-based therapy rescues social deficits in genetic, environmental, and idiopathic mouse models of ASD. This rescue depends upon the vagus nerve as well as the oxytocinergic and dopaminergic signaling in the brain.
in Neuron on December 03, 2018 12:00 AM.
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The effect of anesthetic dose on the motor response induced by low-intensity pulsed ultrasound stimulation
Low-intensity pulsed ultrasound stimulation (LIPUS) has been proven to be a noninvasive method with high spatial resolution and deep penetration. Previous studies have qualitatively demonstrated that the elect...
in Most Recent Articles: BMC Neuroscience on December 03, 2018 12:00 AM.
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Editorial Board and Contents

in Trends in Neurosciences on December 01, 2018 12:00 AM.
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Theoretically Sparse, Empirically Dense: New Views on Cerebellar Granule Cells
Cerebellar granule cells are a popular target of neuroanatomical hyperbole, being so small and so numerous. Early theorists proposed unique roles for this vast cell population, ideas that continue to be tested through contemporary approaches. In 2017, a cluster of empirical and theoretical papers offered a fresh and singular look into the functions of granule cells and the computational advantages of their idiosyncratic circuit organization.
in Trends in Neurosciences on December 01, 2018 12:00 AM.
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Taking a Big Step towards Understanding Locomotion
Locomotion is generated by intrinsically oscillating circuits in the spinal cord that are modulated by information from the brain and periphery. In their seminal 1987 publication, Buchanan and Grillner provided for the first time evidence for excitatory spinal neurons receiving inputs from descending commands and sensory afferents, and synapsing onto motoneurons and commissural inhibitory interneurons. These critical findings established the circuit model for central pattern generators incorporating excitatory interneurons’ role in the rhythm-production mechanism.
in Trends in Neurosciences on December 01, 2018 12:00 AM.
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Sonic Hedgehog Signaling is Blue: Insights from the Patched Mutant Mice
The Hedgehog (Hh) pathway is a highly conserved signaling system regulating a range of developmental processes. A 1997 paper by Goodrich and colleagues provided major contributions to understanding the Hh pathway by mutating the gene encoding the Hh receptor, Patched, and thereby developing a mouse model for a human cancer predisposition syndrome, known as Gorlin syndrome. These studies provided one of the first genetically engineered mouse models for brain tumors.
in Trends in Neurosciences on December 01, 2018 12:00 AM.
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The Hard and Soft Wired Nature of the Olfactory Map
Across the animal kingdom, odors are known as potent stimuli that directly steer behavior. In 2007, Hitoshi Sakano and colleagues used the power of mouse genetics to manipulate the odor map in the olfactory bulb. Elegant behavioral, anatomical, and physiological analyses revealed an apparent dichotomy in how the brain interprets the odor map. Their work paved a way to think of behavioral contingencies as part of early olfactory processing, highlighting innate and learned pathways.
in Trends in Neurosciences on December 01, 2018 12:00 AM.
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A Compartmental Model to Investigate Local and Global Ca2+ Dynamics in Astrocytes
Evan Cresswell-Clay, Nathan Crock, Joël Tabak, Gordon Erlebacher
in Frontiers in Computational Neuroscience | New and Recent Articles on November 30, 2018 12:00 PM.
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Tocilizumab treatment for new onset refractory status epilepticus

We investigated the therapeutic potential of the interleukin‐6 receptor inhibitor tocilizumab in 7 patients with new onset refractory status epilepticus (NORSE) who remained refractory to conventional immunotherapy with rituximab (n = 5) or without rituximab (n = 2). Status epilepticus (SE) was terminated after 1 or 2 doses of tocilizumab in 6 patients with a median interval of 3 days from the initiation. They had no recurrence of SE during the observation. However, 2 patients experienced severe adverse events related to infection during the tocilizumab therapy. Further prospective controlled studies are warranted to validate the efficacy and safety of tocilizumab in patients with NORSE. Ann Neurol 2018

in Wiley: Annals of Neurology: Table of Contents on November 30, 2018 11:45 AM.
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Levodopa‐induced dyskinesia in Parkinson disease: Current and evolving concepts

Levodopa‐induced dyskinesia is a common complication in Parkinson disease. Pathogenic mechanisms include phasic stimulation of dopamine receptors, nonphysiological levodopa‐to‐dopamine conversion in serotonergic neurons, hyperactivity of corticostriatal glutamatergic transmission, and overstimulation of nicotinic acetylcholine receptors on dopamine‐releasing axons. Delay in initiating levodopa is no longer recommended, as dyskinesia development is a function of disease duration rather than cumulative levodopa exposure. We review current and in‐development treatments for peak‐dose dyskinesia but suggest that improvements in levodopa delivery alone may reduce its future prevalence. Ann Neurol 2018

in Wiley: Annals of Neurology: Table of Contents on November 30, 2018 11:45 AM.
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Meningeal inflammation and cortical demyelination in acute multiple sclerosis

Objective

Cortical gray matter (GM) pathology, involving demyelination and neurodegeneration, associated with meningeal inflammation, could be important in determining disability progression in multiple sclerosis (MS). However, we need to know more about how cortical demyelination, neurodegeneration, and meningeal inflammation contribute to pathology at early stages of MS to better predict long‐term outcome.

Methods

Tissue blocks from short disease duration MS (n = 12, median disease duration = 2 years), progressive MS (n = 21, disease duration = 25 years), non‐diseased controls (n = 11), and other neurological inflammatory disease controls (n = 6) were quantitatively analyzed by immunohistochemistry, immunofluorescence, and in situ hybridization.

Results

Cortical GM demyelination was extensive in some cases of acute MS (range = 1–48% of total cortical GM), and subpial lesions were the most common type (62%). The numbers of activated (CD68⁺) microglia/macrophages were increased in cases with subpial lesions, and the density of neurons was significantly reduced in acute MS normal appearing and lesion GM, compared to controls (p < 0.005). Significant meningeal inflammation and lymphoid‐like structures were seen in 4 of 12 acute MS cases. The extent of meningeal inflammation correlated with microglial/macrophage activation (p < 0.05), but not the area of cortical demyelination, reflecting the finding that lymphoid‐like structures were seen adjacent to GM lesions as well as areas of partially demyelinated/remyelinated, cortical GM.

Interpretation

Our findings demonstrate that cortical demyelination, neuronal loss, and meningeal inflammation are notable pathological hallmarks of acute MS and support the need to identify early biomarkers of this pathology to better predict outcome. Ann Neurol 2018

in Wiley: Annals of Neurology: Table of Contents on November 30, 2018 11:44 AM.
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Genome‐wide meta‐analysis identifies 3 novel loci associated with stroke

We conducted a European‐only and transancestral genome‐wide association meta‐analysis in 72,147 stroke patients and 823,869 controls using data from UK Biobank (UKB) and the MEGASTROKE consortium. We identified an exonic polymorphism in NOS3 (rs1799983, p.Glu298Asp; p = 2.2E‐8, odds ratio [OR] = 1.05, 95% confidence interval [CI] = 1.04–1.07) and variants in an intron of COL4A1 (rs9521634; p = 3.8E‐8, OR = 1.04, 95% CI = 1.03–1.06) and near DYRK1A (rs720470; p = 6.1E‐9, OR = 1.05, 95% CI = 1.03–1.07) at genome‐wide significance for stroke. Effect sizes of known stroke loci were highly correlated between UKB and MEGASTROKE. Using Mendelian randomization, we further show that genetic variation in the nitric oxide synthase–nitric oxide pathway in part affects stroke risk via variation in blood pressure. Ann Neurol 2018

in Wiley: Annals of Neurology: Table of Contents on November 30, 2018 11:43 AM.
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Gender Inequities in the Multiple Sclerosis Community: A Call for Action

in Wiley: Annals of Neurology: Table of Contents on November 30, 2018 11:42 AM.
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Evidence of dysfunction in the visual association cortex in visual snow syndrome

Patients with visual snow syndrome (VS) suffer from a debilitating continuous visual disturbance of unknown mechanism. The present study tested the hypothesis of dysfunctional visual processing using visual evoked potentials. Eighteen patients were compared to age‐matched migraineurs (M) and healthy controls (C) using 2‐way analysis of variance with group (VS, M, C) and gender as factors. Visual evoked potentials from patients with VS demonstrated increased N145 latency (in milliseconds, VS: 152.7 ± 7.9 vs M: 145.3 ± 9.8 vs C: 145.5 ± 9.4; F = 3.28; p = 0.046) and reduced N75–P100 amplitudes (in microvolts, VS: 7.4 ± 3.5 vs M: 12.5 ± 4.7 vs C: 10.8 ± 3.4; F = 3.16; p = 0.051). Dunnett post hoc analysis was significant for all comparisons between VS and controls. These findings are in agreement with the idea that the primary disturbance in VS is a dysfunction of the visual association cortex. Ann Neurol 2018

in Wiley: Annals of Neurology: Table of Contents on November 30, 2018 11:42 AM.
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Biallelic COLGALT1 variants are associated with cerebral small vessel disease

Objective

Approximately 5% of cerebral small vessel diseases are hereditary, which include COL4A1/COL4A2‐related disorders. COL4A1/COL4A2 encode type IV collagen α1/2 chains in the basement membranes of cerebral vessels. COL4A1/COL4A2 mutations impair the secretion of collagen to the extracellular matrix, thereby resulting in vessel fragility. The diagnostic yield for COL4A1/COL4A2 variants is around 20 to 30%, suggesting other mutated genes might be associated with this disease. This study aimed to identify novel genes that cause COL4A1/COL4A2‐related disorders.

Methods

Whole exome sequencing was performed in 2 families with suspected COL4A1/COL4A2‐related disorders. We validated the role of COLGALT1 variants by constructing a 3‐dimensional structural model, evaluating collagen β (1‐O) galactosyltransferase 1 (ColGalT1) protein expression and ColGalT activity by Western blotting and collagen galactosyltransferase assays, and performing in vitro RNA interference and rescue experiments.

Results

Exome sequencing demonstrated biallelic variants in COLGALT1 encoding ColGalT1, which was involved in the post‐translational modification of type IV collagen in 2 unrelated patients: c.452 T > G (p.Leu151Arg) and c.1096delG (p.Glu366Argfs*15) in Patient 1, and c.460G > C (p.Ala154Pro) and c.1129G > C (p.Gly377Arg) in Patient 2. Three‐dimensional model analysis suggested that p.Leu151Arg and p.Ala154Pro destabilized protein folding, which impaired enzymatic activity. ColGalT1 protein expression and ColGalT activity in Patient 1 were undetectable. RNA interference studies demonstrated that reduced ColGalT1 altered COL4A1 secretion, and rescue experiments showed that mutant COLGALT1 insufficiently restored COL4A1 production in cells compared with wild type.

Interpretation

Biallelic COLGALT1 variants cause cerebral small vessel abnormalities through a common molecular pathogenesis with COL4A1/COL4A2‐related disorders. Ann Neurol 2018

in Wiley: Annals of Neurology: Table of Contents on November 30, 2018 11:41 AM.
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Vagus nerve stimulation modulates the cranial trigeminal autonomic reflex

Objective

The trigeminal autonomic reflex plays an important role in primary headache syndromes. Noninvasive vagal nerve stimulation (nVNS) may be an effective modulator of this reflex.

Methods

Twenty‐two healthy volunteers underwent kinetic oscillation stimulation (KOS) of the left nostril as a reliable trigger of the trigeminal autonomic reflex. Previous to KOS, left cervical nVNS, sham simulation, or no stimulation was applied. Lacrimation was quantified using the standardized Schirmer ll test.

Results

Treatment with cervical nVNS significantly reduced lacrimation between no stimulation and nVNS on the ipsilateral side (minute 5: p = 0.026, ηp ² = 0.85, 95% confidence interval [CI] = 1.39–18.04; no stimulation: minute 5, 14.4 ± 9.3 mm; nVNS: minute 5, 4.7 ± 8.6 mm, mean ± standard deviation) as well as between sham stimulation and nVNS (minute 5: p = 0.030, ηp ² = 0.85, 95% CI = 1.04–17.24; sham: minute 5, 13.9 ± 6.4 mm). On the contralateral side, no significant increase between baseline and KOS was observed for nVNS (minute 5: p = 0.614, d = 0.12, 95% CI = −7.09 to 4.31; minute 5, 1.4 ± 11.5 mm) compared to both sham stimulation (minute 5: p = 0.023, d = 0.57, 95% CI = −11.46 to −0.96; minute 5, 6.2 ± 10.9 mm) and no stimulation (minute 5: p < 0.030, d = 0.62, 95% CI = −13.45 to −0.81; minute 5, 7.1 ± 11.4 mm).

Interpretation

Cervical nVNS resulted in a robust bilateral reduction of provoked lacrimation. This effect could be mediated either by direct bilateral activation of structures such as the nucleus of the solitary tract or by a top‐down modulation via the hypothalamus. Ann Neurol 2018

in Wiley: Annals of Neurology: Table of Contents on November 30, 2018 11:40 AM.
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Simultaneous Acquisition of Multicolor Information From Neural Circuits in Resin-Embedded Samples
Miao Ren, Jiaojiao Tian, Peilin Zhao, Jialiang Luo, Zhao Feng, Hui Gong, Xiangning Li
in Frontiers in Neuroscience | Neural Technology section | New and Recent Articles on November 30, 2018 06:00 AM.
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Complements lead to insults

Complements lead to insults
Complements lead to insults, Published online: 30 November 2018; doi:10.1038/s41583-018-0099-8
Two studies show that tau pathology drives the expression of complement molecules that in turn promote the phagocytosis of synapses and neuroinflammation.
in Nature Reviews Neuroscience - Issue - nature.com science feeds on November 30, 2018 12:00 AM.
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Synaptic, Mitochondrial, and Lysosomal Dysfunction in Parkinson’s Disease
The discovery of genetic forms of Parkinson’s disease (PD) has highlighted the importance of the autophagy/lysosomal and mitochondrial/oxidative stress pathways in disease pathogenesis. However, recently identified PD-linked genes, including DNAJC6 (auxilin), SYNJ1 (synaptojanin 1), and the PD risk gene SH3GL2 (endophilin A1), have also highlighted disruptions in synaptic vesicle endocytosis (SVE) as a significant contributor to disease pathogenesis. Additionally, the roles of other PD genes such as LRRK2, PRKN, and VPS35 in the regulation of SVE are beginning to emerge.
in Trends in Neurosciences on November 30, 2018 12:00 AM.
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Cilostazol decreases duration of spreading depolarization and spreading ischemia after aneurysmal subarachnoid hemorrhage

Objective

Traditionally, angiographic vasospasm (aVS) has been thought to cause delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). However, successful treatment of aVS alone does not result in improved neurological outcome. Therefore, there may be other potential causes of poor neurological outcome, including spreading depolarization (SD). A recent study showed beneficial effects of cilostazol on DCI and neurological outcome. The present prospective clinical trial and experimental study focused on effects of cilostazol on SDs.

Methods

Fifty aSAH patients were treated with clip ligation and randomly assigned to a cilostazol (n = 23) or control group (n = 27). Effects of cilostazol on DCI, aVS, and SDs, measured with subdural electrodes, were examined. The effect of cilostazol on SD‐induced perfusion deficits (spreading ischemia) was assessed in an aSAH‐mimicking model.

Results

There was a trend for less DCI in the cilostazol group, but it did not reach our threshold for statistical significance (13.0% vs 40.0%, odds ratio = 0.266, 95% confidence interval [CI] = 0.059–1.192, p = 0.084). However, the total SD‐induced depression duration per recording day (22.2 vs 30.2 minutes, β = −251.905, 95% CI = −488.458 to −15.356, p = 0.043) and the occurrence of isoelectric SDs (0 vs 4 patients, β = −0.916, 95% CI = −1.746 to −0.085, p = 0.037) were significantly lower in the cilostazol group. In rats, cilostazol significantly shortened SD‐induced spreading ischemia compared to vehicle (Student t test, difference = 30.2, 95% CI = 5.3–55.1, p = 0.020).

Interpretation

Repair of the neurovascular response to SDs by cilostazol, as demonstrated in the aSAH‐mimicking model, may be a promising therapy to control DCI. Ann Neurol 2018; 1–13

in Wiley: Annals of Neurology: Table of Contents on November 29, 2018 08:00 PM.
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Temporal control of Drosophila central nervous system development
Rosa Linda Miyares | Tzumin Lee
in Current Opinion in Neurobiology - Just Published on November 29, 2018 06:00 PM.
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Uncovering Biologically Coherent Peripheral Signatures of Health and Risk for Alzheimer’s Disease in the Aging Brain
Brandalyn C. Riedel, Madelaine Daianu, Greg Ver Steeg, Adam Mezher, Lauren E. Salminen, Aram Galstyan, Paul M. Thompson, Alzheimer’s Disease Neuroimaging Initiative
in Frontiers in Aging Neuroscience | New and Recent Articles on November 29, 2018 06:00 PM.
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Sex Differences in Abnormal Intrinsic Functional Connectivity After Acute Mild Traumatic Brain Injury
Shan Wang, Liuxun Hu, Jieli Cao, Wenmin Huang, Chuanzhu Sun, Dongdong Zheng, Zhuonan Wang, Shuoqiu Gan, Xuan Niu, Chenghui Gu, Guanghui Bai, Limei Ye, Danbin Zhang, Nu Zhang, Bo Yin, Ming Zhang, Lijun Bai
in Frontiers in Neural Circuits | New and Recent Articles on November 29, 2018 06:00 PM.
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The HDAC6 Inhibitor Trichostatin A Acetylates Microtubules and Protects Axons From Excitotoxin-Induced Degeneration in a Compartmented Culture Model
Kelsey Hanson, Nan Tian, James C. Vickers, Anna E. King
in Frontiers in Neuroscience | Neurodegeneration section | New and Recent Articles on November 29, 2018 12:00 PM.
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N‐acetylcysteine targets 5 lipoxygenase‐derived, toxic lipids and can synergize with prostaglandin E2 to inhibit ferroptosis and improve outcomes following hemorrhagic stroke in mice

Objectives

N‐acetylcysteine (NAC) is a clinically approved thiol‐containing redox modulatory compound currently in trials for many neurological and psychiatric disorders. Although generically labeled as an “antioxidant,” poor understanding of its site(s) of action is a barrier to its use in neurological practice. Here, we examined the efficacy and mechanism of action of NAC in rodent models of hemorrhagic stroke.

Methods

Hemin was used to model ferroptosis and hemorrhagic stroke in cultured neurons. Striatal infusion of collagenase was used to model intracerebral hemorrhage (ICH) in mice and rats. Chemical biology, targeted lipidomics, arachidonate 5‐lipoxygenase (ALOX5) knockout mice, and viral‐gene transfer were used to gain insight into the pharmacological targets and mechanism of action of NAC.

Results

NAC prevented hemin‐induced ferroptosis by neutralizing toxic lipids generated by arachidonate‐dependent ALOX5 activity. NAC efficacy required increases in glutathione and is correlated with suppression of reactive lipids by glutathione‐dependent enzymes such as glutathione S‐transferase. Accordingly, its protective effects were mimicked by chemical or molecular lipid peroxidation inhibitors. NAC delivered postinjury reduced neuronal death and improved functional recovery at least 7 days following ICH in mice and can synergize with clinically approved prostaglandin E₂ (PGE₂).

Interpretation

NAC is a promising, protective therapy for ICH, which acted to inhibit toxic arachidonic acid products of nuclear ALOX5 that synergized with exogenously delivered protective PGE₂ in vitro and in vivo. The findings provide novel insight into a target for NAC, beyond the generic characterization as an antioxidant, resulting in neuroprotection and offer a feasible combinatorial strategy to optimize efficacy and safety in dosing of NAC for treatment of neurological disorders involving ferroptosis such as ICH. Ann Neurol 2018;00:1‐19

in Wiley: Annals of Neurology: Table of Contents on November 29, 2018 09:27 AM.
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Levodopa‐induced dyskinesia in Parkinson disease: Sleep matters

Objective

The spectrum of clinical symptom changes during the course of Parkinson disease (PD). Levodopa therapy, while offering remarkable control of classical motor symptoms, causes abnormal involuntary movements as the disease progresses. This levodopa‐induced dyskinesia (LID) has been associated with abnormal cortical plasticity. Because slow wave activity (SWA) of nonrapid eye movement (NREM) sleep underlies adjustment of cortical excitability, we sought to elucidate the relationship between this physiological process and LID.

Methods

Thirty‐six patients at different stages of PD underwent whole‐night video polysomnography–high‐density electroencephalography (vPSG‐hdEEG), preceded by 1 week of actigraphy. To represent the broad spectrum of the disease, patients were divided into 3 groups by disease stage—(1) de novo (n = 9), (2) advanced (n = 13), and (3) dyskinetic (DYS; n = 14)—were compared to an age‐matched control group (n = 12). The SWA‐NREM content of the vPSG‐hdEEG was then temporally divided into 10 equal parts, from T1 to T10, and power and source analyses were performed. T2‐T3‐T4 were considered early sleep and were compared to T7‐T8‐T9, representing late sleep.

Results

We found that all groups, except the DYS group, manifested a clear‐cut SWA decrease between early and late sleep.

Interpretation

Our data demonstrate a strong pathophysiological association between sleep and PD. Given that SWA may be a surrogate for synaptic strength, our data suggest that DYS patients do not have adequate synaptic downscaling. Further analysis is needed to determine the effect of drugs that can enhance cortical SWA in LID. Ann Neurol 2018; 1–13

in Wiley: Annals of Neurology: Table of Contents on November 29, 2018 09:25 AM.
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Alterations of NURR1 and Cytokines in the Peripheral Blood Mononuclear Cells: Combined Biomarkers for Parkinson’s Disease
Tianbai Li, Zhaofei Yang, Song Li, Cheng Cheng, Bairong Shen, Weidong Le
in Frontiers in Aging Neuroscience | New and Recent Articles on November 29, 2018 06:00 AM.
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Active Haptic Exploration of Softness: Indentation Force Is Systematically Related to Prediction, Sensation and Motivation
Alexandra Lezkan, Anna Metzger, Knut Drewing
in Frontiers in Integrative Neuroscience | New and Recent Articles on November 29, 2018 06:00 AM.
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Quantification of Signal-to-Noise Ratio in Cerebral Cortex Recordings Using Flexible MEAs With Co-localized Platinum Black, Carbon Nanotubes, and Gold Electrodes
Alex Suarez-Perez, Gemma Gabriel, Beatriz Rebollo, Xavi Illa, Anton Guimerà-Brunet, Javier Hernández-Ferrer, Maria Teresa Martínez, Rosa Villa, Maria V. Sanchez-Vives
in Frontiers in Neuroscience | Neural Technology section | New and Recent Articles on November 29, 2018 06:00 AM.
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PKCε phosphorylation regulates the mitochondrial translocation of ATF2 in ischemia-induced neurodegeneration
Global cerebral ischemia triggers neurodegeneration in the hippocampal CA1 region, but the mechanism of neuronal death remains elusive. The epsilon isoform of protein kinase C (PKCε) has recently been identifi...
in Most Recent Articles: BMC Neuroscience on November 29, 2018 12:00 AM.
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Dyskinesia and brain-derived neurotrophic factor levels after long-term levodopa and nicotinic receptor agonist treatments in female mice with near-total unilateral dopaminergic denervation
The treatment of Parkinson’s disease is often complicated by levodopa-induced dyskinesia (LID). Nicotinic acetylcholine receptor agonists can alleviate LID in animal models but may be less effective in conditi...
in Most Recent Articles: BMC Neuroscience on November 29, 2018 12:00 AM.
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Serum soluble TREM2 as a biomarker for incident dementia: the Hisayama Study

Abstract

Objective

To investigate the association between serum soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a soluble type of an innate immune receptor expressed on the microglia, and the risk of dementia.

Methods

A total of 1,349 Japanese community‐residents aged 60 and older without dementia were followed prospectively for 10 years (2002‐2012). Serum sTREM2 levels were quantified by using an enzyme‐linked immunosorbent assay and divided into quartiles. Cox proportional hazards model was used to estimate the hazard ratios (HRs) of serum sTREM2 levels on the risk of dementia.

Results

During the follow‐up, 300 subjects developed all‐cause dementia; 193 had Alzheimer's disease (AD), and 85 had vascular dementia (VaD). The age‐ and sex‐adjusted incidences of all‐cause dementia, AD, and VaD elevated significantly with higher serum sTREM2 levels (all P for trend <0.012). These associations were not altered after adjustment for confounding factors, including high‐sensitive C‐reactive protein. Subjects with the highest quartile of serum sTREM2 levels had significantly higher multivariable‐adjusted risks of developing all‐cause dementia, AD, and VaD than those with the lowest quartile (HR=2.03, 95% CI=1.39‐2.97, P<0.001 for all‐cause dementia; HR=1.62, 95% CI=1.02‐2.55, P=0.04 for AD; HR=2.85, 95% CI=1.35‐6.02, P=0.006 for VaD). No significant heterogeneity in the association of serum sTREM2 levels with the development of dementia was observed among the other risk‐factor subgroups (all P for heterogeneity >0.11).

Interpretations

The present findings suggest a significant association between increased serum sTREM2 levels and the risk of developing all‐cause dementia, AD, and VaD in the general elderly Japanese population.

This article is protected by copyright. All rights reserved.

in Wiley: Annals of Neurology: Table of Contents on November 28, 2018 08:00 PM.
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Altered Topological Properties of Gray Matter Structural Covariance Networks in Minimal Hepatic Encephalopathy
Tian-Xiu Zou, Lilan She, Chuanyin Zhan, Yong-Qing Gao, Hua-Jun Chen
in Frontiers in Neuroanatomy | New and Recent Articles on November 28, 2018 06:00 PM.
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Blood Markers in Healthy-Aged Nonagenarians: A Combination of High Telomere Length and Low Amyloidβ Are Strongly Associated With Healthy Aging in the Oldest Old
Gorka Fernández-Eulate, Ainhoa Alberro, Maider Muñoz-Culla, Miren Zulaica, Mónica Zufiría, Myriam Barandiarán, Igone Etxeberria, José Javier Yanguas, Maria Mercedes Gallardo, Nora Soberón, Ana María Lacosta, Virginia Pérez-Grijalba, Jesús Canudas, Noelia Fandos, Pedro Pesini, Manuel Sarasa, Begoña Indakoetxea, Fermin Moreno, Itziar Vergara, David Otaegui, Maria Blasco, Adolfo López de Munain
in Frontiers in Aging Neuroscience | New and Recent Articles on November 28, 2018 06:00 PM.
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A Cell Atlas for the Mouse Brain
Csaba Erö, Marc-Oliver Gewaltig, Daniel Keller, Henry Markram
in Frontiers in Neuroinformatics | New and Recent Articles on November 28, 2018 12:00 PM.
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Predicting the Development of Normal-Appearing White Matter With Radiomics in the Aging Brain: A Longitudinal Clinical Study
Yuan Shao, Zhonghua Chen, Shuai Ming, Qin Ye, Zhenyu Shu, Cheng Gong, Peipei Pang, Xiangyang Gong
in Frontiers in Aging Neuroscience | New and Recent Articles on November 28, 2018 06:00 AM.
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Downregulation of Neuronal and Dendritic Connexin36-Made Electrical Synapses Without Glutamatergic Axon Terminals in Spinal Anterior Horn Cells From the Early Stage of Amyotrophic Lateral Sclerosis
Yuko Kobayakawa, Katsuhisa Masaki, Ryo Yamasaki, Wataru Shiraishi, Shotaro Hayashida, Shintaro Hayashi, Koichi Okamoto, Takuya Matsushita, Jun-ichi Kira
in Frontiers in Neuroscience | Neurodegeneration section | New and Recent Articles on November 28, 2018 06:00 AM.
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Decreased Intrinsic Functional Connectivity of the Salience Network in Drug-Naïve Patients With Obsessive-Compulsive Disorder
Yun-Hui Chen, Su-Fang Li, Dan Lv, Gui-Dong Zhu, Yu-Hua Wang, Xin Meng, Qiang Hu, Cheng-Chong Li, Liang-Tang Zhang, Xiang-Ping Chu, Xiao-Ping Wang, Ping Li
in Frontiers in Neuroscience | Brain Imaging Methods section | New and Recent Articles on November 28, 2018 06:00 AM.
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Why Do Durations in Musical Rhythms Conform to Small Integer Ratios?
Andrea Ravignani, Bill Thompson, Massimo Lumaca, Manon Grube
in Frontiers in Computational Neuroscience | New and Recent Articles on November 28, 2018 06:00 AM.
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Do flies like fizz?

Do flies like fizz?
Do flies like fizz?, Published online: 28 November 2018; doi:10.1038/s41583-018-0103-3
Do flies like fizz?
in Nature Reviews Neuroscience - Issue - nature.com science feeds on November 28, 2018 12:00 AM.
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Imagine no fear

Imagine no fear
Imagine no fear, Published online: 28 November 2018; doi:10.1038/s41583-018-0102-4
Imagine no fear
in Nature Reviews Neuroscience - Issue - nature.com science feeds on November 28, 2018 12:00 AM.
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Model potential

Model potential
Model potential, Published online: 28 November 2018; doi:10.1038/s41583-018-0101-5
Model potential
in Nature Reviews Neuroscience - Issue - nature.com science feeds on November 28, 2018 12:00 AM.
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Merkel cells touch a nerve

Merkel cells touch a nerve
Merkel cells touch a nerve, Published online: 28 November 2018; doi:10.1038/s41583-018-0100-6
Merkel cells touch a nerve
in Nature Reviews Neuroscience - Issue - nature.com science feeds on November 28, 2018 12:00 AM.
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Neuronal Constituents and Putative Interactions Within the Drosophila Ellipsoid Body Neuropil
Jaison Jiro Omoto, Bao-Chau Minh Nguyen, Pratyush Kandimalla, Jennifer Kelly Lovick, Jeffrey Michael Donlea, Volker Hartenstein
in Frontiers in Neural Circuits | New and Recent Articles on November 27, 2018 06:00 PM.
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The Emerging Role of Altered Cerebellar Synaptic Processing in Alzheimer’s Disease
Eriola Hoxha, Pellegrino Lippiello, Fabio Zurlo, Ilaria Balbo, Rita Santamaria, Filippo Tempia, Maria Concetta Miniaci
in Frontiers in Aging Neuroscience | New and Recent Articles on November 27, 2018 06:00 PM.
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Astrocyte–Neuron Networks: A Multilane Highway of Signaling for Homeostatic Brain Function
Sara Mederos, Candela González-Arias, Gertrudis Perea
in Frontiers in Synaptic Neuroscience | New and Recent Articles on November 27, 2018 12:00 PM.
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In vivo X-Nuclear MRS Imaging Methods for Quantitative Assessment of Neuroenergetic Biomarkers in Studying Brain Function and Aging
Xiao-Hong Zhu, Wei Chen
in Frontiers in Aging Neuroscience | New and Recent Articles on November 27, 2018 06:00 AM.
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Long-Term Effects of Early Life Seizures on Endogenous Local Network Activity of the Mouse Neocortex
Pavlos Rigas, Charalambos Sigalas, Maria Nikita, Ani Kaplanian, Konstantinos Armaos, Leonidas Jordan Leontiadis, Christos Zlatanos, Aspasia Kapogiannatou, Charoula Peta, Anna Katri, Irini Skaliora
in Frontiers in Synaptic Neuroscience | New and Recent Articles on November 27, 2018 06:00 AM.
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Editorial: Modulating Cortical Dynamics in Language, Speech and Music
Gesa Hartwigsen, Mathias Scharinger, Daniela Sammler
in Frontiers in Integrative Neuroscience | New and Recent Articles on November 27, 2018 06:00 AM.
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Population Coding and Correlated Variability in Electrosensory Pathways
Volker Hofmann, Maurice J. Chacron
in Frontiers in Integrative Neuroscience | New and Recent Articles on November 27, 2018 06:00 AM.
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Disrupted Balance of Long- and Short-Range Functional Connectivity Density in Type 2 Diabetes Mellitus: A Resting-State fMRI Study
Daihong Liu, Lihua Chen, Shanshan Duan, Xuntao Yin, Wu Yang, Yanshu Shi, Jiuquan Zhang, Jian Wang
in Frontiers in Neuroscience | Brain Imaging Methods section | New and Recent Articles on November 27, 2018 06:00 AM.
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Imbalance of Functional Connectivity and Temporal Entropy in Resting-State Networks in Autism Spectrum Disorder: A Machine Learning Approach
Robert X. Smith, Kay Jann, Mirella Dapretto, Danny J. J. Wang
in Frontiers in Neuroscience | Brain Imaging Methods section | New and Recent Articles on November 27, 2018 06:00 AM.
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Dose-Dependent Effects of Closed-Loop tACS Delivered During Slow-Wave Oscillations on Memory Consolidation
Aaron P. Jones, Jaehoon Choe, Natalie B. Bryant, Charles S. H. Robinson, Nicholas A. Ketz, Steven W. Skorheim, Angela Combs, Melanie L. Lamphere, Bradley Robert, Hope A. Gill, Melissa D. Heinrich, Michael D. Howard, Vincent P. Clark, Praveen K. Pilly
in Frontiers in Neuroscience | Neural Technology section | New and Recent Articles on November 27, 2018 06:00 AM.
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Evaluation of Changes in the Motor Network Following BCI Therapy Based on Graph Theory Analysis
Mohsen Mazrooyisebdani, Veena A. Nair, Po-Ling Loh, Alexander B. Remsik, Brittany M. Young, Brittany S. Moreno, Keith C. Dodd, Theresa J. Kang, Justin C. William, Vivek Prabhakaran
in Frontiers in Neuroscience | Neural Technology section | New and Recent Articles on November 27, 2018 06:00 AM.
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Antiepileptic Drug of Levetiracetam Decreases Centrotemporal Spike-Associated Activation in Rolandic Epilepsy
Qirui Zhang, Fang Yang, Zheng Hu, Qiang Xu, Boris C. Bernhardt, Wei Quan, Qian Li, Zhiqiang Zhang, Guangming Lu
in Frontiers in Neuroscience | Brain Imaging Methods section | New and Recent Articles on November 27, 2018 06:00 AM.
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Publisher Correction: Enhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease

Publisher Correction: Enhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease
Publisher Correction: Enhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease, Published online: 27 November 2018; doi:10.1038/s41593-018-0277-z
Publisher Correction: Enhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease
in Nature Neuroscience - Issue - nature.com science feeds on November 27, 2018 12:00 AM.
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Boosting a bad signal

Boosting a bad signal
Boosting a bad signal, Published online: 27 November 2018; doi:10.1038/s41583-018-0095-z
Dopamine released in the rodent prefrontal cortex increases the signal-to-noise ratio of responses to aversive stimuli that are transmitted to the periaqueductal grey.
in Nature Reviews Neuroscience - Issue - nature.com science feeds on November 27, 2018 12:00 AM.
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Structural Connectivity of the Anterior Cingulate Cortex, Claustrum, and the Anterior Insula of the Mouse
Houman Qadir, Samuel R. Krimmel, Chaoqi Mu, Alexandros Poulopoulos, David A. Seminowicz, Brian N. Mathur
in Frontiers in Neuroanatomy | New and Recent Articles on November 26, 2018 06:00 PM.
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Support Vector Machines, Multidimensional Scaling and Magnetic Resonance Imaging Reveal Structural Brain Abnormalities Associated With the Interaction Between Autism Spectrum Disorder and Sex
Andrei Irimia, Xiaoyu Lei, Carinna M. Torgerson, Zachary J. Jacokes, Sumiko Abe, John D. Van Horn
in Frontiers in Computational Neuroscience | New and Recent Articles on November 26, 2018 06:00 PM.
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ADNP Regulates Cognition: A Multitasking Protein
Illana Gozes
in Frontiers in Neuroscience | Neurodegeneration section | New and Recent Articles on November 26, 2018 06:00 AM.
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Natriuretic Peptides in Post-mortem Brain Tissue and Cerebrospinal Fluid of Non-demented Humans and Alzheimer’s Disease Patients
Simin Mahinrad, Marjolein Bulk, Isabelle van der Velpen, Ahmed Mahfouz, Willeke van Roon-Mom, Neal Fedarko, Sevil Yasar, Behnam Sabayan, Diana van Heemst, Louise van der Weerd
in Frontiers in Neuroscience | Neurodegeneration section | New and Recent Articles on November 26, 2018 06:00 AM.
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Kinetic Modeling of pH-Dependent Oxidation of Dopamine by Iron and Its Relevance to Parkinson's Disease
Yingying Sun, A. Ninh Pham, Dominic J. Hare, T. David Waite
in Frontiers in Neuroscience | Neurodegeneration section | New and Recent Articles on November 26, 2018 06:00 AM.
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Xolotl: An Intuitive and Approachable Neuron and Network Simulator for Research and Teaching
Srinivas Gorur-Shandilya, Alec Hoyland, Eve Marder
in Frontiers in Neuroinformatics | New and Recent Articles on November 26, 2018 06:00 AM.

Planet Neuroscience

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Abstract

Abstract

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ABSTRACT

Objective

Methods

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