Nature Neuroscience Contents: March 2016 Volume 19 Number 3, pp 347 - 522

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Deadlines: Bursary: 23 Feb/ Abstract: 8 Mar/ Registration: 22 Mar   Advertisement Open for Submissions An interdisciplinary journal dedicated to publishing high-quality open research relevant to all aspects of schizophrenia and psychosis. Explore the benefits of submitting your next research article.    Advertisement Key Issues in Alzheimer's Disease- a community forum  Nature Neuroscience presents a forum on Alzheimer's Disease research. ACCESS NOW to view videos of our panel event at SfN 2015, read related articles for free, and post questions for our editors and featured experts. Produced with support from  Eli Lilly and Company and vTv Therapeutics     Focus Top Focus on stress Focus issue: March 2016 Volume 19, No 3 Contents Editorial Commentary Perspectives Reviews Editorial Top Focus on neural computation and theory   p347 doi:10.1038/nn.4261 We present a special issue focusing on recent advances in computation- and theory-driven approaches to neuroscience that inform a host of biophysical and mechanistic models. Commentary Top Conceptual and technical advances define a key moment for theoretical neuroscience   pp348 - 349 Anne K Churchland and L F Abbott doi:10.1038/nn.4255 Theoretical approaches have long shaped neuroscience, but current needs for theory are elevated and prospects for advancement are bright. Advances in measuring and manipulating neurons demand new models and analyses to guide interpretation. Advances in theoretical neuroscience offer new insights into how signals evolve across areas and new approaches for connecting population activity with behavior. These advances point to a global understanding of brain function based on a hybrid of diverse approaches. Perspectives Top Building functional networks of spiking model neurons   pp350 - 355 L F Abbott, Brian DePasquale and Raoul-Martin Memmesheimer doi:10.1038/nn.4241 The networks used by computer scientists and by modelers in neuroscience frequently consider unit activities as continuous. Neurons, however, com­municate primarily through discontinuous spiking. This Perspective offers a unifying view of the current methods for transferring our ability to construct functional networks from continuous to more realistic spiking network models. Using goal-driven deep learning models to understand sensory cortex   pp356 - 365 Daniel L K Yamins and James J DiCarlo doi:10.1038/nn.4244 Recent computational neuroscience developments have used deep neural networks to model neural responses in higher visual areas. This Perspective describes key algorithmic underpinnings in computer vision and artificial intelligence that have contributed to this progress and outlines how deep networks could drive future improvements in understanding sensory cortical processing. Confidence and certainty: distinct probabilistic quantities for different goals   pp366 - 374 Alexandre Pouget, Jan Drugowitsch and Adam Kepecs doi:10.1038/nn.4240 The authors use recent probabilistic theories of neural computation to argue that confidence and certainty are not identical concepts. They propose precise mathematical definitions for both of these concepts and discuss putative neural representations. Reviews Top Efficient codes and balanced networks   pp375 - 382 Sophie Dèneve and Christian K Machens doi:10.1038/nn.4243 Despite representing a minority of cortical cells, inhibitory neurons deeply shape cortical responses. Inhibitory currents closely track excitatory currents, opening only brief windows of opportunity for a neuron to fire. This explains the variability of cortical spike trains, but may also, paradoxically, render a spiking network maximally efficient and precise. The mechanics of state-dependent neural correlations   pp383 - 393 Brent Doiron, Ashok Litwin-Kumar, Robert Rosenbaum, Gabriel K Ocker and Krešimir Josi? doi:10.1038/nn.4242 The state of the nervous system shifts constantly. Most studies focus on how state determines the average neural response, with little attention to the trial-to-trial fluctuations of brain activity. We review recent theoretical advances in modeling the physiological mechanisms responsible for state-dependent modulations in the correlated fluctuations of neuronal populations. Computational principles of memory   pp394 - 403 Rishidev Chaudhuri and Ila Fiete doi:10.1038/nn.4237 What are the challenges associated with storing information over time in the brain? Here the authors explore the computational principles by which biological memory might be built. They develop a high-level view of shared problems and themes in short- and long-term memory and highlight questions for future research. Computational psychiatry as a bridge from neuroscience to clinical applications   pp404 - 413 Quentin J M Huys, Tiago V Maia and Michael J Frank doi:10.1038/nn.4238 The complexity of problems and data in psychiatry requires powerful computational approaches. Computational psychiatry is an emerging field encompassing mechanistic theory-driven models and theoretically agnostic data-driven analyses that use machine-learning techniques. Clinical applications will benefit from relating theoretically meaningful process variables to complex psychiatric outcomes through data-driven techniques. News and Views Top Illuminating next-generation brain therapies   pp414 - 416 Emily Ferenczi and Karl Deisseroth doi:10.1038/nn.4232 A clinical trial inspired and guided by optogenetics experiments in rodents reports the outcome of targeted transcranial magnetic stimulation in patients suffering from cocaine addiction. See also: Article by Knafo et al. Targeting PTEN interactions for Alzheimer's disease   pp416 - 418 Samuel Frere and Inna Slutsky doi:10.1038/nn.4248 Depression of AMPA receptor-mediated synaptic currents and impairment of long-term potentiation, triggered by amyloid-β, are the hallmarks of Alzheimer's pathophysiology. These dysfunctions are now linked to upregulated PDZ domain–dependent PTEN translocation to spines, contributing to cognitive deficits in model mice. See also: Article by Eshel et al. Gaining on reward prediction errors   pp418 - 419 Nathan F Parker and Ilana B Witten doi:10.1038/nn.4246 In this issue of Nature Neuroscience, Eshel et al. characterize the homogeneity with which individual dopamine neurons encode reward prediction error, a teaching signal that is thought to be crucial for associative learning. See also: Article by Franke et al. Schizophrenia and brain volume genetic covariation   p419 P Alexander Arguello doi:10.1038/nn0316-419 See also: Article by Franke et al. Neuroscience JOBS of the week Faculty Position In Neuroscience - Open Rank University of Rochester School of Medicine & Dentistry - Department of Neuroscience Faculty Recruitment (Department of Developmental Biology and Neuroscience) Graduate School of Life Sciences, Tohoku University Postdoctoral Fellow in Coen- Cagli Laboratory in Computational Neuroscience Albert Einstein College of Medicine of Yeshiva University (AECOM) Director, Integrative Neuroscience Center Purdue University Post doctoral fellow in neuroscience Uppsala University More Science jobs from Neuroscience EVENT Applying Computational Modelling to Clinical Neuroscience 06.04.16 Buckinghamshire, UK More science events from Articles Top Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept   pp420 - 431 Barbara Franke, Jason L Stein, Stephan Ripke, Verneri Anttila, Derrek P Hibar et al. doi:10.1038/nn.4228 The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap. See also: News and Views by Parker & Witten Metabotropic NMDA receptor signaling couples Src family kinases to pannexin-1 during excitotoxicity   pp432 - 442 Nicholas L Weilinger, Alexander W Lohman, Brooke D Rakai, Evelyn M M Ma, Jennifer Bialecki et al. doi:10.1038/nn.4236 The loss of nerve cells in the brain is the main event causing life-long deficits and neurological problems after stroke. Weilinger et al. show that NMDA receptors cause nerve cell death during stroke in an unexpected way. Although they require ligand binding and recruitment of downstream pannexin channels, NMDA receptors do not use the receptor's ion channel. PTEN recruitment controls synaptic and cognitive function in Alzheimer's models   pp443 - 453 Shira Knafo, Cristina Sánchez-Puelles, Ernest Palomer, Igotz Delgado, Jonathan E Draffin et al. doi:10.1038/nn.4225 In this study, the authors show that PTEN alters synaptic function after PDZ-dependent recruitment into spines induced by amyloid-β. This mechanism is crucial for pathogenesis, as preventing PTEN-PDZ interactions renders neurons resistant to amyloid-β and rescues cognitive function in Alzheimer's disease models. This suggests that PTEN is a critical effector of the synaptic pathology associated with Alzheimer's disease. See also: News and Views by Ferenczi & Deisseroth PV plasticity sustained through D1/5 dopamine signaling required for long-term memory consolidation   pp454 - 464 Smitha Karunakaran, Ananya Chowdhury, Flavio Donato, Charles Quairiaux, Christoph M Michel et al. doi:10.1038/nn.4231 This study shows that learning-induced plasticity of local parvalbumin (PV) basket cells is specifically required for long-term, but not short to intermediate-term, memory consolidation in mice. PV plasticity depends on local D1/5 dopamine receptor signaling 12-14 h after acquisition for its continuance, ensuring enhanced sharp-wave ripple densities and memory consolidation. Separate circuitries encode the hedonic and nutritional values of sugar   pp465 - 470 Luis A Tellez, Wenfei Han, Xiaobing Zhang, Tatiana L Ferreira, Isaac O Perez et al. doi:10.1038/nn.4224 Unlike artificial sweeteners, sugar promotes ingestive behavior via both gustatory and post-ingestive pathways. Tellez et al. find that separate basal ganglia circuits mediate the hedonic and nutritional actions of sugar. They demonstrate that sugar recruits a dedicated striatofugal pathway that acts to prioritize calorie-seeking over taste quality. Nicotinic receptors in the ventral tegmental area promote uncertainty-seeking   pp471 - 478 Jérémie Naudé, Stefania Tolu, Malou Dongelmans, Nicolas Torquet, Sébastien Valverde et al. doi:10.1038/nn.4223 The role of subcortical acetylcholine in decision-making under uncertainty is ill-defined. By combining genetic tools, computational modeling and a new multi-armed bandit task for mice, the authors show that nicotinic acetylcholine receptors expressed in the ventral tegmental area drive the motivation to seek reward uncertainty. Dopamine neurons share common response function for reward prediction error   pp479 - 486 Neir Eshel, Ju Tian, Michael Bukwich and Naoshige Uchida doi:10.1038/nn.4239 Dopamine neurons in the ventral tegmental area are thought to signal reward prediction error. The authors show that these neurons respond with striking homogeneity during classical conditioning. All dopamine neurons appear to calculate reward prediction error similarly, enabling robust and consistent broadcasting of this signal throughout the brain. See also: News and Views by Frere & Slutsky On-going computation of whisking phase by mechanoreceptors   pp487 - 493 Avner Wallach, Knarik Bagdasarian and Ehud Ahissar doi:10.1038/nn.4221 Wallach et al. use closed-loop artificial whisking in anesthetized rats to show that vibrissal mechanoreceptors extract phase information from on-going whisker kinematics in a frequency- and amplitude-invariant manner. Brainstem paralemniscal neurons preserve this phase information while filtering out information about whisker offset; lemniscal neurons preserve both types of information. Resources Top Epigenomic annotation of gene regulatory alterations during evolution of the primate brain   pp494 - 503 Marit W Vermunt, Sander C Tan, Bas Castelijns, Geert Geeven, Peter Reinink et al. doi:10.1038/nn.4229 Gene-regulatory elements are drivers of evolutionary divergence, yet where these are located and which are evolutionarily relevant is unclear. In this work, large-scale epigenomic analysis of human, rhesus and chimpanzee brain tissue allowed the identification of human-specific gene-regulatory changes that contributed to the emergence of the human brain. Microglial brain region–dependent diversity and selective regional sensitivities to aging   pp504 - 516 Kathleen Grabert, Tom Michoel, Michail H Karavolos, Sara Clohisey, J Kenneth Baillie et al. doi:10.1038/nn.4222 Heterogeneity within distinct cell populations resident in the central nervous system is increasingly recognized as important for functional diversity, plasticity and sensitivity to neurological disease. The authors demonstrate genome-wide diversity of microglia dependent on brain localization in the young adult and show that aging of microglia occurs in a regionally variable manner. Technical Report Top Engineering microdeletions and microduplications by targeting segmental duplications with CRISPR   pp517 - 522 Derek J C Tai, Ashok Ragavendran, Poornima Manavalan, Alexei Stortchevoi, Catarina M Seabra et al. doi:10.1038/nn.4235 Recurrent, reciprocal genomic disorders due to non-allelic homologous recombination (NAHR) are a major cause of human disease. The authors developed a CRISPR/Cas9 genome engineering method that directly targets segmental duplications and efficiently mimics the NAHR-mediated mechanism of microdeletion and microduplication that occurs in vivo using 16p11.2 and 15q13.3 as proof-of-principle models. 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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