Nature Neuroscience Contents: November 2016 Volume 19 Number 11, pp 1381 - 1536

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Advertisement Nikon invites you to visit www.seemorethanbefore.com for a sneak peek at our latest imaging innovation. Sign up to receive updates leading up to the big November 9 reveal, and be sure to visit the Nikon booth at the Neuroscience 2016 Meeting in San Diego to see the new system in action. To See More Than Before, click here. TABLE OF CONTENTS November 2016 Volume 19, Issue 11 Focus Editorial Correspondence Commentaries Reviews News and Views Articles Resource Advertisement   FREE TRIAL: New Neuropsychiatric Disorder Models For a limited time, validate Taconic Biosciences' new neuropsychiatric disorder models in your research facility for free.   Models with chromosomal deletions orthologous to human 15q13.3, 22q11.2, or 1q21.1. Useful for screening novel drug candidates for treating schizophrenia, autism spectrum disorders, epilepsy and other neuropsychiatric disorders. Try FREE now Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Nature Outlook: Lysosomal Storage Disorders Lysosomal storage disorders are individually rare but collectively common. The study of these diseases is not only leading to better treatments, but also revealing many of the secrets of this underappreciated organelle.  Access the Outlook > Produced with support from:  Alexion Pharmaceuticals, Inc. Ultragenyx Pharmaceutical Inc. Produced with support of a grant from: Shire plc BioMarin Pharmaceutical Inc     Advertisement nature.com webcasts Springer Nature presents a custom webcast on: uDISCO for whole organs and organisms: A new way of large sample imaging Date: Thursday October 27, 2016 Time: 8AM PDT, 11AM EDT, 4PM BST, 5PM CEST Register for FREE Sponsored by: Bitplane LaVision Biotech Andor Technology     Advertisement Nature Human Behaviour Covering the scope of human behavior   Nature Human Behaviour will publish research of outstanding significance into any aspect of human behaviour: its psychological, biological, and social bases, as well as its origins, development, and disorders. Need access at your workplace or institution?  Click here to recommend site license access to your librarian.   Focus Top Focus on psychiatric disorders Focus issue: November 2016 Volume 19, No 11 Focus Home Editorial Correspondence Commentaries Perspectives Reviews News and Views   Editorial Top Focus on psychiatric disorders   pp1381 - 1382 doi:10.1038/nn.4434 Nature Neuroscience presents a Focus issue highlighting progress in basic and clinical sciences advancing mental health research. Correspondence Top Back to basics: luring industry back into neuroscience   pp1383 - 1384 Steven E Hyman doi:10.1038/nn.4429 An obsession with producing and validating models (face, construct, predictive validity) has led many of us down a deep rabbit hole, thinking about models instead of mechanisms. Advances in the human genetics and neurobiology of brain disorders create exciting new opportunities, but only if we can get back to basics. Commentaries Top On being a circuit psychiatrist   pp1385 - 1386 Joshua A Gordon doi:10.1038/nn.4419 Recent technological advancements in the study of neural circuits provide reasons to be optimistic that novel treatments for psychiatric illnesses are just around the corner. Maximizing the chances of translating these advancements into real improvements in patient care requires a carefully considered road map. Psychiatric distress in animals versus animal models of psychiatric distress   pp1387 - 1389 Robert M Sapolsky doi:10.1038/nn.4397 Primatology research suggests that other primates suffer from crippling depression or anxiety, implying that these diseases' roots pre-date human history. At the same time, some realms of psychiatry remain uniquely human. Recognizing the similarities and dissimilarities between us and other primates is essential in studying animal models of psychiatric disease. The origin and natural history of autism spectrum disorders   pp1390 - 1391 James C Harris doi:10.1038/nn.4427 Refined social phenotyping of syndromic and idiopathic forms of autism, combined with advances in genetics, animal models of syndromes and brain imaging, may facilitate discovery of shared brain mechanisms that will lead to new treatments. The reversal of social deficits in animal models is promising for eventual translation into therapeutics. Translating genome-wide association findings into new therapeutics for psychiatry   pp1392 - 1396 Gerome Breen, Qingqin Li, Bryan L Roth, Patricio O'Donnell, Michael Didriksen et al. doi:10.1038/nn.4411 The Psychiatric Genomics Consortium is aiming to analyze data from >1 million individuals. This is already leading to hundreds of new genetic findings across psychiatric disorders with the potential to restart largely stalled psychiatric drug development pipelines. This paper outlines key questions and plans to translate findings into new therapeutics. Reviews Top The road to precision psychiatry: translating genetics into disease mechanisms   pp1397 - 1407 Michael J Gandal, Virpi Leppa, Hyejung Won, Neelroop N Parikshak and Daniel H Geschwind doi:10.1038/nn.4409 Recently, robust identification of hundreds of genetic variants associated with risk for neuropsychiatric disease has prompted new challenges in understanding their biological impact within an individual. The authors provide a framework for interpretation of genetic risk variants to uncover disease mechanisms and facilitate therapeutic development. Lessons learned from studying syndromic autism spectrum disorders   pp1408 - 1417 Yehezkel Sztainberg and Huda Y Zoghbi doi:10.1038/nn.4420 Autism spectrum disorders are highly heterogeneous and include both idiopathic and syndromic forms. Sztainberg and Zoghbi discuss insights gained from studying syndromic autism spectrum disorders and their potential contribution to our understanding of the molecular pathways critical for normal cognitive and social development, as well as the relevance to idiopathic autism. Using model systems to understand errant plasticity mechanisms in psychiatric disorders   pp1418 - 1425 Bruno B Averbeck and Matthew V Chafee doi:10.1038/nn.4413 Animal models have failed to yield new treatments for psychiatric disorders. Some psychiatric disorders may result from pathology in plasticity mechanisms. Therefore, understanding plasticity mechanisms in model systems may provide insight into the disordered processes in patients. News and Views Top Rare variants are common in schizophrenia   pp1426 - 1428 Jacob Gratten doi:10.1038/nn.4422 A large DNA sequencing study of schizophrenia finds more evidence that rare inherited coding mutations across many genes contribute to risk of the disorder. This has important implications for geneticists and neuroscientists alike. See also: Article by Genovese et al. Brains, genes and power   pp1428 - 1430 Frank W Albert doi:10.1038/nn.4424 Gene expression data from more than 500 human brains shed light on the molecular consequences of genetic variation that contributes to schizophrenia. See also: Article by Fromer et al. When size matters: CHD8 in autism   pp1430 - 1432 Martin W Breuss and Joseph G Gleeson doi:10.1038/nn.4431 Recent models studying loss of the mouse homolog of the autism-associated gene CHD8 show altered Wnt signaling, cell fate and proliferation. How do these findings shape our understanding of this disease? See also: Article by Durak et al. Neuroscience JOBS of the week Post-Doctoral Fellow in Neuroscience Washington University School of Medicine Post-Doctoral Fellow in Neuroscience, Optogenetics, and Imaging Washington University School of Medicine Neuroscience Faculty Member-University of Illinois at Urbana Champaign University of Illinois at Urbana/Champaign Faculty Position In Theoretical Neuroscience Cold Spring Harbor Laboratory (CSHL) Postdoctoral position in Neuroscience: Neural Circuits underlying behavior Max Planck Society, caesar More Science jobs from Neuroscience EVENT 2nd International Brain Stimulation Conference 5th - 8th March 2017 Barcelona, Spain More science events from Advertisement Labeled Iba1 Antibodies At the request of our customers, Wako's antibody for the microglial marker Iba1, is now available in labeled forms. Choose from 2 types - one conjugated with Biotin and the other with Red Fluorochrome (635). This can eliminate the need for a secondary antibody, and provides reduced background.   Articles Top Increased burden of ultra-rare protein-altering variants among 4,877 individuals with schizophrenia   pp1433 - 1441 Giulio Genovese, Menachem Fromer, Eli A Stahl, Douglas M Ruderfer, Kimberly Chambert et al. doi:10.1038/nn.4402 Using whole-exome sequencing, the authors identified 244,246 coding-sequence and splice-site ultra-rare variants (URVs) and found that gene-disruptive and putatively protein-damaging URVs were significantly more abundant in schizophrenia cases than in controls. The excess of protein-compromising URVs was concentrated in brain-specific genes, particularly in neuronally expressed genes whose proteins are located at the synapse. See also: News and Views by Gratten Gene expression elucidates functional impact of polygenic risk for schizophrenia   pp1442 - 1453 Menachem Fromer, Panos Roussos, Solveig K Sieberts, Jessica S Johnson, David H Kavanagh et al. doi:10.1038/nn.4399 The CommonMind Consortium sequenced RNA from dorsolateral prefrontal cortex of subjects with schizophrenia (N=258) and control subjects (N=279), creating a resource of gene expression and its genetic regulation. Using this resource, they found that [sim]20% of schizophrenia loci have variants that may contribute to altered gene expression and liability. See also: News and Views by Albert Genome-wide prediction and functional characterization of the genetic basis of autism spectrum disorder   pp1454 - 1462 Arjun Krishnan, Ran Zhang, Victoria Yao, Chandra L Theesfeld, Aaron K Wong et al. doi:10.1038/nn.4353 Autism spectrum disorder is a complex disease with a strong genetic basis that remains under-characterized by current genetics studies. Here, the authors use a computational approach based on a human brain-specific gene network to predict autism-associated genes across the genome and further delineate their functional and developmental characteristics. Genome-wide, integrative analysis implicates microRNA dysregulation in autism spectrum disorder   pp1463 - 1476 Ye E Wu, Neelroop N Parikshak, T Grant Belgard and Daniel H Geschwind doi:10.1038/nn.4373 The authors performed genome-wide microRNA (miRNA) expression profiling in post-mortem brains from individuals with autism spectrum disorder (ASD) and controls, and identified miRNAs and co-regulated modules perturbed in ASD. Chd8 mediates cortical neurogenesis via transcriptional regulation of cell cycle and Wnt signaling   pp1477 - 1488 Omer Durak, Fan Gao, Yea Jin Kaeser-Woo, Richard Rueda, Anthony J Martorell et al. doi:10.1038/nn.4400 De novo mutations in CHD8 are associated with autism spectrum disorder, but the basic biology of CHD8 remains poorly understood. Here the authors find that Chd8 knockdown during cortical development results in defective neural progenitor proliferation and differentiation that ultimately manifests in abnormal neuronal morphology and behaviors in adult mice. See also: News and Views by Breuss & Gleeson Ucn3 and CRF-R2 in the medial amygdala regulate complex social dynamics   pp1489 - 1496 Yair Shemesh, Oren Forkosh, Mathias Mahn, Sergey Anpilov, Yehezkel Sztainberg et al. doi:10.1038/nn.4346 Social encounters are associated with varying degrees of stress. The authors show that modulation of stress system components in the medial amygdala alters preference for familiar vs. novel conspecifics. Inhibition of the relevant circuit in a group of familiar mice kept under semi-natural conditions increased pro-social behavior. Histone deacetylase 3 associates with MeCP2 to regulate FOXO and social behavior   pp1497 - 1505 Alexi Nott, Jemmie Cheng, Fan Gao, Yuan-Ta Lin, Elizabeta Gjoneska et al. doi:10.1038/nn.4347 Mutations in MECP2 cause Rett syndrome. The authors show that a MeCP2-HDAC3 complex positively regulates a subset of neuronal genes through FOXO recruitment and deacetylation, and that HDAC3 loss contributes to cognitive and social deficits in mice. Rett-patient-derived cells exhibited similar HDAC3-FOXO-mediated transcriptional impairments and were rescued by gene editing. MeCP2 and histone deacetylases 1 and 2 in dorsal striatum collectively suppress repetitive behaviors   pp1506 - 1512 Melissa Mahgoub, Megumi Adachi, Kanzo Suzuki, Xihui Liu, Ege T Kavalali et al. doi:10.1038/nn.4395 Loss of Hdac1 and Hdac2 in adult brain is detrimental to neuronal survival and triggers dysregulation of Sapap3 in the striatum in a MeCP2-dependent manner that results in an exacerbated repetitive behavior phenotype. Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c   pp1513 - 1522 Yi-Chuan Chen, Hsiao-Ying Kuo, Ulrich Bornschein, Hiroshi Takahashi, Shih-Yun Chen et al. doi:10.1038/nn.4380 Chen et al. found that Foxp2 interacts with Mef2c to wire synaptic circuits linking neocortex to basal ganglia. The study analyzes the basics of circuit wiring underlying vocal communication. 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.    Resource Top Multimodal population brain imaging in the UK Biobank prospective epidemiological study   pp1523 - 1536 Karla L Miller, Fidel Alfaro-Almagro, Neal K Bangerter, David L Thomas, Essa Yacoub et al. doi:10.1038/nn.4393 The UK Biobank combines detailed phenotyping and genotyping with tracking of long-term health outcomes in a large cohort. This study describes the recently launched brain-imaging component that will ultimately scan 100,000 individuals. Results from the first 5,000 subjects are reported, including thousands of associations, population modes and hypothesis-driven results. 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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