Neuron: May 3, 2017 (Volume 94, Issue 3)

[Cell press]( [Facebook]( [Twitter]( [Youtube]( [Google Plus]( [Weibo]( [Issue cover]( [May 03, 2017]( Vol. 94, Iss. 3 [Website]( [Table of Contents]( [Online Now]( [Archive]( Highlights Announcements --------------------------------------------------------------- [Introducing Sneak Peek, a preview of Cell Press papers under review]( Exciting science needs to be shared, and fast. That's why we're introducing [Cell Press Sneak Peek](, a preview of the papers under consideration in our primary research journals. Sneak Peek makes papers discoverable earlier in the publication process—so authors can surface their research quickly and readers can build on their work. [Free Webinar – Cancer, Inflammation and Immunity]( Speakers: Douglas T. Fearon & Mikala Egeblad May 17, 2017, 12 pm EDT Claim your free registration for live or on-demand access today! [Click here to register.]( Featured Article --------------------------------------------------------------- [De Novo Coding Variants Are Strongly Associated with Tourette Disorder]( A. Jeremy Willsey, Thomas V. Fernandez, Dongmei Yu, Robert A. King, Andrea Dietrich, Jinchuan Xing, Stephan J. Sanders, Jeffrey D. Mandell, Alden Y. Huang, Petra Richer, Louw Smith, Shan Dong, Kaitlin E. Samocha, Tourette International Collaborative Genetics (TIC Genetics), Tourette Syndrome Association International Consortium for Genetics (TSAICG), Benjamin M. Neale, Giovanni Coppola, Carol A. Mathews, Jay A. Tischfield, Jeremiah M. Scharf, Matthew W. State, Gary A. Heiman Featured Review --------------------------------------------------------------- [Allosteric Modulation of GPCRs: New Insights and Potential Utility for Treatment of Schizophrenia and Other CNS Disorders]( Daniel J. Foster, P. Jeffrey Conn Online Now --------------------------------------------------------------- [Netrin1 Produced by Neural Progenitors, Not Floor Plate Cells, Is Required for Axon Guidance in the Spinal Cord]( Varadarajan et al. Video Abstracts --------------------------------------------------------------- [De Novo Coding Variants Are Strongly Associated With Tourette Disorder]( New research led by UC San Francisco scientists [Jeremy Willsey and Matthew State]( has identified four likely risk genes with multiple de novo variants connected with Tourette disorder. This discovery promises to further our understanding of the genetic factors contributing to Tourette disorder and point to further gene discoveries using exome studies. [Removing Stressed Mitochondria from Axons Independent of Mitophagy]( [Lin and Cheng et al.]( reveal a new mechanism maintaining axonal mitochondrial integrity by releasing anchoring protein syntaphilin from static dysfunctional mitochondria. This process enables the removal of dysfunctional mitochondria from axons before activation of Parkin-mediated mitophagy under physiological and pathological conditions. Table of Contents Previews --------------------------------------------------------------- [Population Control: Cortical Interneurons Modulate Oligodendrogenesis]( Pratiti Bandopadhayay, Charles D. Stiles During central nervous system development, oligodendrocytes must be formed in proportion to the number of neurons requiring their services. In this issue of Neuron, Voronova et al. show how cortical interneurons modulate oligodendrogenesis through a cytokine-mediated paracrine interaction. [Lethal Giant Lineage Tracing: Mutating Locally, Acting Globally]( Aslam Abbasi Akhtar, Hannah Park, Joshua J. Breunig The generation of neurons and glia from radial glia progenitors is critical to proper neocortical development but the mechanisms regulating their deterministic production are unclear. In this issue of Neuron, Beattie et al. (2017) use elegant MADM-based lineage tracing to demonstrate cell-intrinsic and global functions for Lgl1 during neocortical development. [Epigenomics of Retinal Development in Mice and Humans]( Nicolas Lonfat, Connie Cepko In this issue of Neuron, Aldiri, Xu, et al. (2017) present an analysis of epigenetic changes during retinal development, and use these data to probe reprogramming of retinal iPSC cells, as well as the origin of retinoblastoma cells. [What Do Sensory Organs Tell the Brain?]( Avner Wallach, Satomi Ebara, Ehud Ahissar Understanding how perception emerges depends on the understanding of sensory acquisition by sensory organs. In this issue of Neuron, Severson et al. (2017) present a brilliant leap towards understanding active sensory coding by mechanoreceptors. NeuroView --------------------------------------------------------------- [The BRAINS Program: Transforming Career Development to Advance Diversity and Equity in Neuroscience]( Joyce W. Yen, M. Claire Horner-Devine, Cara Margherio, Sheri J.Y. Mizumori In order to better prepare trainees and advance diversity in neuroscience, career development must move beyond scientific skills. The BRAINS Program’s continuous professional development model positively impacts participants’ careers by fostering a sense of community and creating a counterspace for critical conversations. Reviews --------------------------------------------------------------- [Allosteric Modulation of GPCRs: New Insights and Potential Utility for Treatment of Schizophrenia and Other CNS Disorders]( Daniel J. Foster, P. Jeffrey Conn Allosteric modulators of GPCRs allow selective modulation of GPCR signaling in identified brain circuits with remarkable precision. Foster and Conn review recent advances enabled by these novel compounds as well as their potential utility in the treatment of CNS disorders. [The Mechanisms and Functions of Synaptic Facilitation]( Skyler L. Jackman, Wade G. Regehr Short-term facilitation dynamically strengthens synapses to regulate information transfer through neural circuits. Jackman and Regehr review recent advances in understanding the mechanisms underlying facilitation, which could ultimately clarify the functional and behavioral roles of this widespread form of short-term plasticity. NeuroResource --------------------------------------------------------------- [MUPET—Mouse Ultrasonic Profile ExTraction: A Signal Processing Tool for Rapid and Unsupervised Analysis of Ultrasonic Vocalizations]( Maarten Van Segbroeck, Allison T. Knoll, Pat Levitt, Shrikanth Narayanan Van Segbroeck et al. present open-access software that uses signal processing techniques to perform rapid, unsupervised analysis of mouse ultrasonic vocalization repertoires, including unbiased syllable discovery, new metrics to compare syllable production and use, and syllable time stamp enabling next-step behavioral analyses. Articles --------------------------------------------------------------- [De Novo Coding Variants Are Strongly Associated with Tourette Disorder]( A. Jeremy Willsey, Thomas V. Fernandez, Dongmei Yu, Robert A. King, Andrea Dietrich, Jinchuan Xing, Stephan J. Sanders, Jeffrey D. Mandell, Alden Y. Huang, Petra Richer, Louw Smith, Shan Dong, Kaitlin E. Samocha, Tourette International Collaborative Genetics (TIC Genetics), Tourette Syndrome Association International Consortium for Genetics (TSAICG), Benjamin M. Neale, Giovanni Coppola, Carol A. Mathews, Jay A. Tischfield, Jeremiah M. Scharf, Matthew W. State, Gary A. Heiman Gene discovery by identifying recurrent de novo variants with whole-exome sequencing has proven effective in neurodevelopmental disorders like autism, epilepsy, and intellectual disability. Willsey et al. apply this approach to Tourette disorder, associate de novo variants, and identify genes. [Migrating Interneurons Secrete Fractalkine to Promote Oligodendrocyte Formation in the Developing Mammalian Brain]( Anastassia Voronova, Scott A. Yuzwa, Beatrix S. Wang, Siraj Zahr, Charvi Syal, Jing Wang, David R. Kaplan, Freda D. Miller Voronova et al. show migrating interneurons act in a paracrine fashion to promote the developmental genesis of oligodendrocytes. They show fractalkine is secreted by interneurons and when fractalkine signaling is inhibited, fewer oligodendrocyte lineage cells are made in the cortex. [Mosaic Analysis with Double Markers Reveals Distinct Sequential Functions of Lgl1 in Neural Stem Cells]( Robert Beattie, Maria Pia Postiglione, Laura E. Burnett, Susanne Laukoter, Carmen Streicher, Florian M. Pauler, Guanxi Xiao, Olga Klezovitch, Valeri Vasioukhin, Troy H. Ghashghaei, Simon Hippenmeyer Beattie et al. determined the relative contribution of novel intrinsic Lgl1 gene functions and non-cell-autonomous community effects in neural stem cell proliferation behavior. They found distinct but sequential Lgl1 functions controlling embryonic neurogenesis and postnatal astrocyte and olfactory bulb interneuron generation. [Serotonergic Projections Govern Postnatal Neuroblast Migration]( Diego García-González, Konstantin Khodosevich, Yasuhito Watanabe, Astrid Rollenhagen, Joachim H.R. Lübke, Hannah Monyer García-González and colleagues described a serotonergic modulatory mechanism governing the migration of postnatally generated, SVZ-derived neuroblasts. The authors show that serotonergic axons aligned to migrating neuroblasts control speed and directionality of migration. The mechanism involves calcium signaling via 5HT3A receptors. [The Dynamic Epigenetic Landscape of the Retina During Development, Reprogramming, and Tumorigenesis]( Issam Aldiri, Beisi Xu, Lu Wang, Xiang Chen, Daniel Hiler, Lyra Griffiths, Marc Valentine, Abbas Shirinifard, Suresh Thiagarajan, Andras Sablauer, Marie-Elizabeth Barabas, Jiakun Zhang, Dianna Johnson, Sharon Frase, Xin Zhou, John Easton, Jinghui Zhang, Elaine R. Mardis, Richard K. Wilson, James R. Downing, Michael A. Dyer Aldiri, Xu, and colleagues show in this article how the epigenome of the mouse and human retina changes during development in coordination with transcriptional programs. They also relate those developmental changes to retinoblastoma and epigenetic memory in retina-derived iPSCs. [Structural Bases of Desensitization in AMPA Receptor-Auxiliary Subunit Complexes]( Edward C. Twomey, Maria V. Yelshanskaya, Robert A. Grassucci, Joachim Frank, Alexander I. Sobolevsky Auxiliary subunits tightly regulate AMPA receptor function in excitatory neurotransmission. Twomey et al. elucidate the structural bases for regulation of desensitization in AMPA receptor complexes, where profound changes in interfaces and symmetry of the synaptic receptor domains dictate gating kinetics. [Blood-Brain Barrier Permeability Is Regulated by Lipid Transport-Dependent Suppression of Caveolae-Mediated Transcytosis]( Benjamin J. Andreone, Brian Wai Chow, Aleksandra Tata, Baptiste Lacoste, Ayal Ben-Zvi, Kevin Bullock, Amy A. Deik, David D. Ginty, Clary B. Clish, Chenghua Gu Andreone et al. revealed a key mechanism that explains how the suppression of transcytosis occurs to control BBB permeability. They discovered a single pathway revealing that the lipids transported by Mfsd2a control the formation of caveolae and therefore BBB integrity. [Releasing Syntaphilin Removes Stressed Mitochondria from Axons Independent of Mitophagy under Pathophysiological Conditions]( Mei-Yao Lin, Xiu-Tang Cheng, Prasad Tammineni, Yuxiang Xie, Bing Zhou, Qian Cai, Zu-Hang Sheng Lin and Cheng et al. reveal a new mechanism maintaining axonal mitochondrial integrity by releasing anchoring protein syntaphilin from stressed mitochondria, thus facilitating the removal of dysfunctional mitochondria from axons before activation of Parkin-mediated mitophagy under physiological and pathological conditions. [Conditional Deletion of All Neurexins Defines Diversity of Essential Synaptic Organizer Functions for Neurexins]( Lulu Y. Chen, Man Jiang, Bo Zhang, Ozgun Gokce, Thomas C. Südhof Using conditional deletions of all mouse neurexin genes, Chen et al. show that neurexins are key synaptic organizers that perform synapse-specific functions, ranging from synapse loss to impairments of synaptic transmission and a suppression of action potential-induced calcium influx. [Skilled Movements Require Non-apoptotic Bax/Bak Pathway-Mediated Corticospinal Circuit Reorganization]( Zirong Gu, Najet Serradj, Masaki Ueno, Mishi Liang, Jie Li, Mark L. Baccei, John H. Martin, Yutaka Yoshida Gu et al. find reorganization of corticospinal circuits controlling antagonistic muscle pairs during development. This reorganization requires the activity-dependent, non-apoptotic Bax/Bak-caspase pathway. Mice lacking the Bax/Bak pathway in the motor cortex show defects in corticospinal reorganization and skilled movements. [Chronic Loss of CA2 Transmission Leads to Hippocampal Hyperexcitability]( Roman Boehringer, Denis Polygalov, Arthur J.Y. Huang, Steven J. Middleton, Vincent Robert, Marie E. Wintzer, Rebecca A. Piskorowski, Vivien Chevaleyre, Thomas J. McHugh Boehringer et al. show that silencing CA2 pyramidal cells leads to hyperexcitability in CA3 and a novel pathophysiology manifesting as spatially triggered hippocampal network population discharges. This establishes a key role of CA2-recruited inhibition in CA3 in maintaining hippocampal E/I balance. [Homeostatic Plasticity Shapes Cell-Type-Specific Wiring in the Retina]( Nai-Wen Tien, Florentina Soto, Daniel Kerschensteiner Tien et al. discover circuit-level homeostatic plasticity in the retina. After removal of their dominant bipolar cell input, ONα retinal ganglion cells adjust connectivity with other bipolar cells in cell-type-specific ratios to precisely preserve their light responses. [Active Touch and Self-Motion Encoding by Merkel Cell-Associated Afferents]( Kyle S. Severson, Duo Xu, Margaret Van de Loo, Ling Bai, David D. Ginty, Daniel H. O’Connor Severson, Xu et al. recorded from identified Merkel cell-associated and other primary afferents in behaving mice. Surprisingly, these mechanoreceptor neurons encoded not only the properties of touched objects, but also whisker position, suggesting a dual role in touch and proprioception. [Medial Entorhinal Cortex Selectively Supports Temporal Coding by Hippocampal Neurons]( Nick T.M. Robinson, James B. Priestley, Jon W. Rueckemann, Aaron D. Garcia, Vittoria A. Smeglin, Francesca A. Marino, Howard Eichenbaum Robinson and Priestley et al. combine single-unit recording with large-scale optogenetic inactivation in animals performing a temporal association memory task to assess the role of MEC in the generation of hippocampal temporal, spatial, and object-selective firing fields. Corrections --------------------------------------------------------------- [The Mammalian-Specific Protein Armcx1 Regulates Mitochondrial Transport during Axon Regeneration]( Romain Cartoni, Michael W. Norsworthy, Fengfeng Bei, Chen Wang, Siwei Li, Yiling Zhang, Christopher V. Gabel, Thomas L. Schwarz, Zhigang He [Kinetics of Endogenous CaMKII Required for Synaptic Plasticity Revealed by Optogenetic Kinase Inhibitor]( Hideji Murakoshi, Myung Eun Shin, Paula Parra-Bueno, Erzsebet M. Szatmari, Akihiro C.E. Shibata, Ryohei Yasuda [Update Your Profile]([Terms and Conditions]([Privacy Policy]([Unsubscribe from Email Alert]( This email has been sent from Cell Press, a division of Elsevier Inc., 50 Hampshire Street, 5th Floor, Cambridge, MA 02139, USA. You are receiving this email because you signed up for email alerts for new issues of this journal. For all inquiries, problems or suggestions regarding this service, please contact JournalsOnlineSupport-usa@elsevier.com. Copyright © 2017 Cell Press/Elsevier Inc. All rights reserved.