Nature Neuroscience Contents: April 2016 Volume 19 Number 4, pp 523 - 642

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Advertisement Nature Outlook Cognitive Health This Nature Outlook investigates some of the strategies that can be used to keep our brains in top form when faced with social and biological factors that induce deterioration. Available free online. Produced with support from: Nestlé Research TABLE OF CONTENTS April 2016 Volume 19, Issue 4 News and Views Perspective Review Brief Communications Articles Resource Technical Report Corrigendum Errata Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Nature Publishing Group offers a free open access funding support service to enable authors to discover and apply for article processing charge funding available to them. Visit our website for further advice on the funding options available, and guidance in approaching funders and institutions, or email openaccess@nature.com for more information.    News and Views Top Schizophrenia genetics complements its mechanistic understanding   pp523 - 525 Elizabeth K Ruzzo and Daniel H Geschwind doi:10.1038/nn.4277 Refinement of genetic variants within the major histocompatibility complex reveals three distinct genetic influences on schizophrenia risk and sheds light on the disease's neurobiology. Rare genetic variants and schizophrenia   pp525 - 527 Jonathan Flint doi:10.1038/nn.4271 A study reports mutations in a histone methyltransferase gene, SETD1A, in schizophrenia patients and demonstrates that tens of thousands of people must be screened to provide robust evidence of a gene's involvement in schizophrenia. See also: Article by Singh et al. How (not) to silence long-range projections with light   pp527 - 528 J Simon Wiegert and Thomas G Oertner doi:10.1038/nn.4270 Inhibitory optogenetic tools prevent action potential generation during illumination. A study explores the possibility of squelching already propagating action potentials locally at axon terminals before they trigger neurotransmitter release. See also: Brief Communication by Mahn et al. And the beat goes on: from clock to behavior   pp529 - 530 Matthieu Flourakis and Ravi Allada doi:10.1038/nn.4278 Master circadian clocks in discrete neurons trigger profound daily changes in brain states, such as sleep and wake states. A study now finds a circuit through which these pacemakers act to control daily behavioral rhythms in Drosophila. See also: Article by Cavey et al. Hippogate: a break-in from entorhinal cortex   pp530 - 532 Allyson Alexander and Ivan Soltesz doi:10.1038/nn.4253 Discrimination of neutral from harmful environments is important for survival. But how do salient contextual signals yield persisting memories? A study uncovers a circuit that increases the specificity of hippocampus-based memories. Fight club for mice   p532 Brigitta B Gundersen doi:10.1038/nn0416-532 See also: Article by Falkner et al. Neuroscience JOBS of the week Institute Senior Research Scientist Neuroscience Hit to Lead Medicinal Chemistry The University of Texas MD Anderson Cancer Center Scientific Director and professor of the School for Mental Health and Neuroscience (1,0 fte) Maastricht University (UM) Lab Head Ophthalmology Bayer HealthCare Postdoctoral Researcher University of California, San Diego ( UCSD ) Neurobiologist Rutgers University - New Brunswick More Science jobs from Neuroscience EVENT 5th Champalimaud Neuroscience Symposium 21st - 24th September 2016 Lisbon, Portugal More science events from Perspective Top Thalamus plays a central role in ongoing cortical functioning   pp533 - 541 S Murray Sherman doi:10.1038/nn.4269 In this Perspective, Murray Sherman discusses connectivity in the thalamocortical system, including the evidence that cortical areas are connected in parallel by direct and transthalamic pathways. Because thalamus receives inputs that form collaterals with subcortical motor regions, the author suggests that it may relay efference copy information. Review Top Modeling ALS with motor neurons derived from human induced pluripotent stem cells   pp542 - 553 Samuel Sances, Lucie I Bruijn, Siddharthan Chandran, Kevin Eggan, Ritchie Ho et al. doi:10.1038/nn.4273 In this Review, a collaboration of leading experts in amyotrophic lateral sclerosis (ALS) research present the state of the field regarding the use patient-derived induced pluripotent stem cells to generate motor neurons in vitro. Motor neuron characterization, including transcriptomics, molecular markers, neuron function and electrophysiology, are discussed in the context of maturation and disease. Brief Communications Top Biophysical constraints of optogenetic inhibition at presynaptic terminals   pp554 - 556 Mathias Mahn, Matthias Prigge, Shiri Ron, Rivka Levy and Ofer Yizhar doi:10.1038/nn.4266 Optogenetic inhibition of specific axonal projections is a potentially powerful technique for assessing defined neural pathways' contributions to behavior. The authors report that while optogenetic inhibition can efficiently attenuate presynaptic release, it can under some conditions lead to undesired effects such as depolarization and increased spontaneous release. See also: News and Views by Wiegert & Oertner Hyperactive somatostatin interneurons contribute to excitotoxicity in neurodegenerative disorders   pp557 - 559 Wen Zhang, Lifeng Zhang, Bo Liang, David Schroeder, Zhong-wei Zhang et al. doi:10.1038/nn.4257 Pathogenesis for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) remains largely unknown. Using a mouse model of ALS and FTD, the authors found that somatostatin interneurons in motor cortex were hyperactive. This hyperactivity led to the disinhibition of pyramidal neurons and correlated with signs of excitotoxicity. Ablating somatostatin interneurons restored the excitability of pyramidal cells to a normal level and prevented neurodegeneration. Resilience to chronic stress is mediated by noradrenergic regulation of dopamine neurons   pp560 - 563 Elsa Isingrini, Léa Perret, Quentin Rainer, Bénédicte Amilhon, Elisa Guma et al. doi:10.1038/nn.4245 Dopaminergic neurons in the ventral tegmental area (VTA) contribute to mediating stress susceptibility and resilience. The authors demonstrate that noradrenergic neurons in the locus coeruleus can drive the activity of these dopaminergic VTA neurons to generate a resilient response to chronic stress. Recoding a cocaine-place memory engram to a neutral engram in the hippocampus   pp564 - 567 Stéphanie Trouche, Pavel V Perestenko, Gido M van de Ven, Claire T Bratley, Colin G McNamara et al. doi:10.1038/nn.4250 Subsets of hippocampal neurons store map-like representations of experienced environments. The authors optogenetically silenced a neuronal population active in an environment and saw an alternative map emerge. In a cocaine-paired environment, this approach neutralized drug-place preference, implicating recoding of spatial memory engrams as strategy for alleviating maladaptive behaviors. An excitatory basis for divisive normalization in visual cortex   pp568 - 570 Tatsuo K Sato, Bilal Haider, Michael Hausser and Matteo Carandini doi:10.1038/nn.4249 Increases in synaptic inhibition have been proposed to underlie divisive normalization in distal neural networks. Here, using optogenetic stimulation and intracellular recordings in mouse visual cortex, the authors argue that normalization is a result of a decrease in synaptic excitation. Articles Top Rare loss-of-function variants in SETD1A are associated with schizophrenia and developmental disorders   pp571 - 577 Tarjinder Singh, Mitja I Kurki, David Curtis, Shaun M Purcell, Lucy Crooks et al. doi:10.1038/nn.4267 The authors analyzed the whole-exome sequences of over 16,000 individuals and found that very rare variants predicted to disrupt the SETD1A gene confer substantial risk for schizophrenia. Damaging variants in SETD1A were also associated with diverse, severe developmental disorders, providing an important genetic link between schizophrenia and other neurodevelopmental disorders. See also: News and Views by Flint Fluorescent false neurotransmitter reveals functionally silent dopamine vesicle clusters in the striatum   pp578 - 586 Daniela B Pereira, Yvonne Schmitz, József Mészáros, Paolomi Merchant, Gang Hu et al. doi:10.1038/nn.4252 The authors report the generation of fluorescent false neurotransmitter 200 (FFN200), a new optical probe for selectively monitoring monoamine exocytosis in cultured neurons and brain slices. Using the new tool in combination with Ca2+ imaging, they find functionally silent dopaminergic vesicle clusters in the striatum, with impaired exocytosis at a step downstream from Ca2+ influx. Circadian rhythms in neuronal activity propagate through output circuits   pp587 - 595 Matthieu Cavey, Ben Collins, Claire Bertet and Justin Blau doi:10.1038/nn.4263 Circadian pacemaker neurons help animals synchronize their behavior with 24-hour day-night cycles. The authors identify a neuronal circuit that links Drosophila pacemaker neurons to locomotor activity and sleep centers. They show that the intrinsic neuronal activity rhythms of pacemaker neurons are transmitted through this circuit to generate rhythmic behavior. See also: News and Views by Flourakis & Allada Hypothalamic control of male aggression-seeking behavior   pp596 - 604 Annegret L Falkner, Logan Grosenick, Thomas J Davidson, Karl Deisseroth and Dayu Lin doi:10.1038/nn.4264 The authors show that the ventrolateral aspect of the ventromedial hypothalamus (VMHvl), a region previously implicated in attack behavior, can also drive flexible aggression-seeking behavior. When male mice learn a task to seek out attack opportunities, activity in the VMHvl tracks and bidirectionally modulates the seeking behavior that leads to future attack. See also: News and Views by Gundersen 4-Hz oscillations synchronize prefrontal-amygdala circuits during fear behavior   pp605 - 612 Nikolaos Karalis, Cyril Dejean, Fabrice Chaudun, Suzana Khoder, Robert R Rozeske et al. doi:10.1038/nn.4251 This study demonstrates that fear memory expression is driven by 4-Hz oscillations in prefrontal-amygdala circuits. During fear behavior, prefrontal 4-Hz oscillations lead amygdala and synchronize spiking activity between the two structures. Ultimately, this study identifies 4-Hz oscillations as a physiological signature of fear memories. Explicit information for category-orthogonal object properties increases along the ventral stream   pp613 - 622 Ha Hong, Daniel L K Yamins, Najib J Majaj and James J DiCarlo doi:10.1038/nn.4247 This study shows that the amount of linearly decodable information for categorical-orthogonal object tasks (for example, position, scale, pose, perimeter and aspect ratio) increases up the ventral visual hierarchy, ultimately matching human levels in inferior temporal cortex. It also provides a computational model that explains how this pattern of information arises. Resource Top Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice   pp623 - 633 Peter Langfelder, Jeffrey P Cantle, Doxa Chatzopoulou, Nan Wang, Fuying Gao et al. doi:10.1038/nn.4256 To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington's disease pathogenesis, the authors profiled mRNA in over 600 brain and peripheral tissue samples from Huntington's disease knock-in mice with increasing CAG repeat lengths. Coexpression network analyses reveal 13 striatal and 5 cortical modules that are highly correlated with CAG length and age. Technical Report Top Spike sorting for large, dense electrode arrays   pp634 - 641 Cyrille Rossant, Shabnam N Kadir, Dan F M Goodman, John Schulman, Maximilian L D Hunter et al. doi:10.1038/nn.4268 Silicon microelectrodes are a powerful technique for recording neuronal population activity. Increases in probe size and density make for larger recordable populations, but also require new techniques for processing the resulting data. The authors describe a suite of practical, open source software for spike sorting of large, dense electrode arrays. Corrigendum Top Corrigendum: Stimulus-specific combinatorial functionality of neuronal c-fos enhancers   p642 Jae-Yeol Joo, Katie Schaukowitch, Lukas Farbiak, Gokhul Kilaru and Tae-Kyung Kim doi:10.1038/nn0416-642a Errata Top Erratum: Causal contribution of primate auditory cortex to auditory perceptual decision-making   p642 Joji Tsunada, Andrew S K Liu, Joshua I Gold and Yale E Cohen doi:10.1038/nn0416-642b Erratum: Schizophrenia and brain volume genetic covariation   p642 P Alexander Arguello doi:10.1038/nn0416-642c Top Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. The digital version is available here. Find the latest scientific conferences, courses, meetings and symposia on natureevents.com. For event advertising opportunities across the Nature Publishing Group portfolio please contact natureevents@nature.com More Nature Events

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