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  • Neuropilin-2/PlexinA3 Receptors Associate with GluA1 and Mediate Sema3F-Dependent Homeostatic Scaling in Cortical Neurons
    Neuron (IF 14.024) Pub Date : 2017-11-16
    Qiang Wang, Shu-Ling Chiu, Eleftheria Koropouli, Ingie Hong, Sarah Mitchell, Teresa P. Easwaran, Natalie R. Hamilton, Ahleah S. Gustina, Qianwen Zhu, David D. Ginty, Richard L. Huganir, Alex L. Kolodkin

    Regulation of AMPA-type glutamate receptor (AMPAR) number at synapses is a major mechanism for controlling synaptic strength during homeostatic scaling in response to global changes in neural activity. We show that the secreted guidance cue semaphorin 3F (Sema3F) and its neuropilin-2 (Npn-2)/plexinA3 (PlexA3) holoreceptor mediate homeostatic plasticity in cortical neurons. Sema3F-Npn-2/PlexA3 signaling is essential for cell surface AMPAR homeostatic downscaling in response to an increase in neuronal activity, Npn-2 associates with AMPARs, and Sema3F regulates this interaction. Therefore, Sema3F-Npn-2/PlexA3 signaling controls both synapse development and synaptic plasticity.

    更新日期:2017-11-19
  • Collective Behavior of Place and Non-place Neurons in the Hippocampal Network
    Neuron (IF 14.024) Pub Date : 2017-11-16
    Leenoy Meshulam, Jeffrey L. Gauthier, Carlos D. Brody, David W. Tank, William Bialek

    Discussions of the hippocampus often focus on place cells, but many neurons are not place cells in any given environment. Here we describe the collective activity in such mixed populations, treating place and non-place cells on the same footing. We start with optical imaging experiments on CA1 in mice as they run along a virtual linear track and use maximum entropy methods to approximate the distribution of patterns of activity in the population, matching the correlations between pairs of cells but otherwise assuming as little structure as possible. We find that these simple models accurately predict the activity of each neuron from the state of all the other neurons in the network, regardless of how well that neuron codes for position. Our results suggest that understanding the neural activity may require not only knowledge of the external variables modulating it but also of the internal network state.

    更新日期:2017-11-19
  • Lateral Orbitofrontal Inactivation Dissociates Devaluation-Sensitive Behavior and Economic Choice
    Neuron (IF 14.024) Pub Date : 2017-11-16
    Matthew P.H. Gardner, Jessica S. Conroy, Michael H. Shaham, Clay V. Styer, Geoffrey Schoenbaum

    How do we choose between goods that have different subjective values, like apples and oranges? Neuroeconomics proposes that this is done by reducing complex goods to a single unitary value to allow comparison. This value is computed “on the fly” from the underlying model of the goods space, allowing decisions to meet current needs. This is termed “model-based” behavior to distinguish it from pre-determined, habitual, or “model-free” behavior. The lateral orbitofrontal cortex (OFC) supports model-based behavior in rats and primates, but whether the OFC is necessary for economic choice is less clear. Here we tested this question by optogenetically inactivating the lateral OFC in rats in a classic model-based task and during economic choice. Contrary to predictions, inactivation disrupted model-based behavior without affecting economic choice.

    更新日期:2017-11-19
  • The Wnt Inhibitor Apcdd1 Coordinates Vascular Remodeling and Barrier Maturation of Retinal Blood Vessels
    Neuron (IF 14.024) Pub Date : 2017-11-16
    Jenna Mazzoni, Julian R. Smith, Sanjid Shahriar, Tyler Cutforth, Bernardo Ceja, Dritan Agalliu

    Coordinating angiogenesis with acquisition of tissue-specific properties in endothelial cells is essential for vascular function. In the retina, endothelial cells form a blood-retina barrier by virtue of tight junctions and low transcytosis. While the canonical Norrin/Fz4/Lrp5/6 pathway is essential for angiogenesis, vascular remodeling, and barrier maturation, how these diverse processes are coordinated remains poorly understood. Here we demonstrate that Apcdd1, a negative regulator of Wnt/β-catenin signaling, is expressed in retinal endothelial cells during angiogenesis and barrier formation.Apcdd1-deficient mice exhibit a transient increase in vessel density at ages P10–P12 due to delayed vessel pruning. Moreover,Apcdd1mutant endothelial cells precociously form the paracellular component of the barrier. Conversely, mice that overexpress Apcdd1 in retina endothelial cells have reduced vessel density but increased paracellular barrier permeability. Apcdd1 thus serves to precisely modulate Wnt/Norrin signaling activity in the retinal endothelium and coordinate the timing of both vascular pruning and barrier maturation.

    更新日期:2017-11-19
  • Endogenous Gαq-Coupled Neuromodulator Receptors Activate Protein Kinase A
    Neuron (IF 14.024) Pub Date : 2017-11-16
    Yao Chen, Adam J. Granger, Trinh Tran, Jessica L. Saulnier, Alfredo Kirkwood, Bernardo L. Sabatini

    Protein kinase A (PKA) integrates inputs from G-protein-coupled neuromodulator receptors to modulate synaptic and cellular function. Gαs signaling stimulates PKA activity, whereas Gαi inhibits PKA activity. Gαq, on the other hand, signals through phospholipase C, and it remains unclear whether Gαq-coupled receptors signal to PKA in their native context. Here, using two independent optical reporters of PKA activity in acute mouse hippocampus slices, we show that endogenous Gαq-coupled muscarinic acetylcholine receptors activate PKA. Mechanistically, this effect is mediated by parallel signaling via either calcium or protein kinase C. Furthermore, multiple Gαq-coupled receptors modulate phosphorylation by PKA, a classical Gαs/Gαi effector. Thus, these results highlight PKA as a biochemical integrator of three major types of GPCRs and necessitate reconsideration of classic models used to predict neuronal signaling in response to the large family of Gαq-coupled receptors.

    更新日期:2017-11-19
  • Discrete Circuits Support Generalized versus Context-Specific Vocal Learning in the Songbird
    Neuron (IF 14.024) Pub Date : 2017-11-16
    Lucas Y. Tian, Michael S. Brainard

    Motor skills depend on the reuse of individual gestures in multiple sequential contexts (e.g., a single phoneme in different words). Yet optimal performance requires that a given gesture be modified appropriately depending on the sequence in which it occurs. To investigate the neural architecture underlying such context-dependent modifications, we studied Bengalese finch song, which, like speech, consists of variable sequences of “syllables.” We found that when birds are instructed to modify a syllable in one sequential context, learning generalizes across contexts; however, if unique instruction is provided in different contexts, learning is specific for each context. Using localized inactivation of a cortical-basal ganglia circuit specialized for song, we show that this balance between generalization and specificity reflects a hierarchical organization of neural substrates. Primary motor circuitry encodes a core syllable representation that contributes to generalization, while top-down input from cortical-basal ganglia circuitry biases this representation to enable context-specific learning.

    更新日期:2017-11-19
  • Neuropilin-2/PlexinA3 Receptors Associate with GluA1 and Mediate Sema3F-Dependent Homeostatic Scaling in Cortical Neurons
    Neuron (IF 14.024) Pub Date : 2017-11-16
    Qiang Wang, Shu-Ling Chiu, Eleftheria Koropouli, Ingie Hong, Sarah Mitchell, Teresa P. Easwaran, Natalie R. Hamilton, Ahleah S. Gustina, Qianwen Zhu, David D. Ginty, Richard L. Huganir, Alex L. Kolodkin
    更新日期:2017-11-19
  • Collective Behavior of Place and Non-place Neurons in the Hippocampal Network
    Neuron (IF 14.024) Pub Date : 2017-11-16
    Leenoy Meshulam, Jeffrey L. Gauthier, Carlos D. Brody, David W. Tank, William Bialek
    更新日期:2017-11-19
  • Lateral Orbitofrontal Inactivation Dissociates Devaluation-Sensitive Behavior and Economic Choice
    Neuron (IF 14.024) Pub Date : 2017-11-16
    Matthew P.H. Gardner, Jessica S. Conroy, Michael H. Shaham, Clay V. Styer, Geoffrey Schoenbaum
    更新日期:2017-11-19
  • The Wnt Inhibitor Apcdd1 Coordinates Vascular Remodeling and Barrier Maturation of Retinal Blood Vessels
    Neuron (IF 14.024) Pub Date : 2017-11-16
    Jenna Mazzoni, Julian R. Smith, Sanjid Shahriar, Tyler Cutforth, Bernardo Ceja, Dritan Agalliu
    更新日期:2017-11-19
  • Endogenous Gαq-Coupled Neuromodulator Receptors Activate Protein Kinase A
    Neuron (IF 14.024) Pub Date : 2017-11-16
    Yao Chen, Adam J. Granger, Trinh Tran, Jessica L. Saulnier, Alfredo Kirkwood, Bernardo L. Sabatini
    更新日期:2017-11-19
  • Discrete Circuits Support Generalized versus Context-Specific Vocal Learning in the Songbird
    Neuron (IF 14.024) Pub Date : 2017-11-16
    Lucas Y. Tian, Michael S. Brainard
    更新日期:2017-11-19
  • GABAergic Synaptogenesis: A Case for Cooperation
    Neuron (IF 14.024) Pub Date : 2017-11-15
    Jean-Marc Fritschy, Shiva K. Tyagarajan
    更新日期:2017-11-16
  • Epimetronomics: m6A Marks the Tempo of Corticogenesis
    Neuron (IF 14.024) Pub Date : 2017-11-15
    Nathan C. Boles, Sally Temple
    更新日期:2017-11-16
  • A Local Rebalancing Act Leads to Global Benefit
    Neuron (IF 14.024) Pub Date : 2017-11-15
    Ju Lu, Yi Zuo

    Barnes et al. (2017) reveal that in the visual cortex of sensory-deprived mice, dendritic spine enlargement correlates with recent spine loss from the same dendritic branch. Such branch-specific homeostatic plasticity highlights dendritic branches as key computational units.

    更新日期:2017-11-16
  • Good Vibrations: Resting-State Functional Connectivity Reflects Entrainment of Vasomotion
    Neuron (IF 14.024) Pub Date : 2017-11-15
    Allen W. Chan, Timothy H. Murphy

    In this issue ofNeuron,Mateo et al. (2017) suggest that hemodynamic measures of resting-state functional connectivity in cortex are reporting the consequences of entrainment of arteriole vasomotion by neuronal activity.

    更新日期:2017-11-16
  • A Synaptic Basis for GLP-1 Action in the Brain
    Neuron (IF 14.024) Pub Date : 2017-11-15
    Sandrine Lefort, Matthias H. Tschöp, Cristina García-Cáceres
    更新日期:2017-11-16
  • The Spatiotemporal Organization of the Striatum Encodes Action Space
    Neuron (IF 14.024) Pub Date : 2017-11-15
    Andreas Klaus, Gabriela J. Martins, Vitor B. Paixao, Pengcheng Zhou, Liam Paninski, Rui M. Costa

    (Neuron 95, 1171–1180; August 30, 2017)

    更新日期:2017-11-16
  • Single-Cell Profiling of an In Vitro Model of Human Interneuron Development Reveals Temporal Dynamics of Cell Type Production and Maturation
    Neuron (IF 14.024) Pub Date : 2017-11-15
    Jennie L. Close, Zizhen Yao, Boaz P. Levi, Jeremy A. Miller, Trygve E. Bakken, Vilas Menon, Jonathan T. Ting, Abigail Wall, Anne-Rachel Krostag, Elliot R. Thomsen, Angel M. Nelson, John K. Mich, Rebecca D. Hodge, Soraya I. Shehata, Ian A. Glass, Susan Bort, Nadiya V. Shapovalova, N. Kiet Ngo, Joshua S. Grimley, John W. Phillips, Carol L. Thompson, Sharad Ramanathan, Ed Lein

    (Neuron 93, 1035–1048; March 8, 2017)

    更新日期:2017-11-16
  • 更新日期:2017-11-16
  • Gender Equality from a European Perspective: Myth and Reality
    Neuron (IF 14.024) Pub Date : 2017-11-15
    Patricia C. Salinas, Claudia Bagni
    更新日期:2017-11-16
  • Orbitofrontal Cortex: A Neural Circuit for Economic Decisions
    Neuron (IF 14.024) Pub Date : 2017-11-15
    Camillo Padoa-Schioppa, Katherine E. Conen
    更新日期:2017-11-16
  • Building Bridges through Science
    Neuron (IF 14.024) Pub Date : 2017-11-15
    Thomas Lissek, Michelle Adams, John Adelman, Ehud Ahissar, Mohammed Akaaboune, Huda Akil, Mustafa al’Absi, Fazal Arain, Juan Carlos Arango-Lasprilla, Deniz Atasoy, Jesus Avila, Ashraf Badawi, Hilmar Bading, Abdul Mannan Baig, Jimena Baleriola, Carlos Belmonte, Ilaria Bertocchi, Heinrich Betz, Colin Blakemore, Olaf Blanke, Philipp Boehm-Sturm, Tobias Bonhoeffer, Paolo Bonifazi, Nils Brose, Patrizia Campolongo, Tansu Celikel, Cathy C. Chang, Ta-Yuan Chang, Ami Citri, Hollis T. Cline, Jesus M. Cortes, Kathleen Cullen, Kellie Dean, José M. Delgado-Garcia, Mathieu Desroches, John F. Disterhoft, John E. Dowling, Andreas Draguhn, Sherif F. El-Khamisy, Abdeljabbar El Manira, S. Ather Enam, Juan M. Encinas, Asier Erramuzpe, José A. Esteban, Isabel Fariñas, Edmond Fischer, Izumi Fukunaga, Iñigo Gabilondo, Detlev Ganten, Albert Gidon, Juan Carlos Gomez-Esteban, Paul Greengard, Valery Grinevich, Agnés Gruart, Roger Guillemin, Ahmad R. Hariri, Bassem Hassan, Michael Häusser, Yasunori Hayashi, Natasha K. Hussain, Adnan Abdul Jabbar, Mohamed Jaber, Reinhardt Jahn, Essam Mohammed Janahi, Mohamed Kabbaj, Helmut Kettenmann, Merel Kindt, Shira Knafo, Georg Köhr, Shoji Komai, Harm Krugers, Bernd Kuhn, Nouria Lakhdar Ghazal, Matthew E. Larkum, Mickey London, Beat Lutz, Carlos Matute, Luis Martinez-Millan, Mouna Maroun, James McGaugh, Ahmed A. Moustafa, Anwar Nasim, Klaus-Armin Nave, Erwin Neher, Karoly Nikolich, Tiago Outeiro, Lucy M. Palmer, Olga Penagarikano, Isabel Perez-Otano, Donald W. Pfaff, Bruno Poucet, Atta-ur Rahman, Pedro Ramos-Cabrer, Ali Rashidy-Pour, Richard J. Roberts, Serafim Rodrigues, Joshua R. Sanes, Andreas T. Schaefer, Menahem Segal, Idan Segev, Saad Shafqat, Nikhat Ahmed Siddiqui, Hermona Soreq, Eduardo Soriano-García, Rainer Spanagel, Rolf Sprengel, Greg Stuart, Thomas C. Südhof, Jan Tønnesen, Mario Treviño, Basim M. Uthman, J. Craig Venter, Alexei Verkhratsky, Craig Weiss, Torsten N. Wiesel, Emre Yaksi, Ofer Yizhar, Larry J. Young, Paul Young, Nasser H. Zawia, José L. Zugaza, Mazahir T. Hasan
    更新日期:2017-11-16
  • Local Order within Global Disorder: Synaptic Architecture of Visual Space
    Neuron (IF 14.024) Pub Date : 2017-11-02
    Benjamin Scholl, Daniel E. Wilson, David Fitzpatrick

    Substantial evidence at the subcellular level indicates that the spatial arrangement of synaptic inputs onto dendrites could play a significant role in cortical computations, but how synapses of functionally defined cortical networks are arranged within the dendrites of individual neurons remains unclear. Here we assessed one-dimensional spatial receptive fields of individual dendritic spines within individual layer 2/3 neuron dendrites. Spatial receptive field properties of dendritic spines were strikingly diverse, with no evidence of large-scale topographic organization. At a fine scale, organization was evident: neighboring spines separated by less than 10 μm shared similar spatial receptive field properties and exhibited a distance-dependent correlation in sensory-driven and spontaneous activity patterns. Fine-scale dendritic organization was supported by the fact that functional groups of spines defined by dimensionality reduction of receptive field properties exhibited non-random dendritic clustering. Our results demonstrate that functional synaptic clustering is a robust feature existing at a local spatial scale.

    更新日期:2017-11-02
  • Kinetics of Releasable Synaptic Vesicles and Their Plastic Changes at Hippocampal Mossy Fiber Synapses
    Neuron (IF 14.024) Pub Date : 2017-11-02
    Mitsuharu Midorikawa, Takeshi Sakaba

    Hippocampal mossy fiber boutons (hMFBs) are presynaptic terminals displaying various forms of synaptic plasticity. The presynaptic mechanisms underlying synaptic plasticity still remain poorly understood. Here, we have combined high temporal resolution measurements of presynaptic capacitance and excitatory postsynaptic currents (EPSCs) to measure the kinetics of exocytosis. In addition, total internal reflection fluorescence (TIRF) microscopy was employed to directly visualize dynamics of single synaptic vesicles adjacent to the plasma membrane at high spatial resolution. Readily releasable vesicles mostly consisted of already-tethered vesicles in the TIRF field. Vesicle replenishment had fast and slow phases, and TIRF imaging suggests that the fast phase depends on vesicle priming from already-tethered vesicles. Application of cyclic AMP (cAMP), a molecule crucial for LTP, mainly increases the vesicular release probability rather than the number of readily releasable vesicles or their replenishment rate, likely by changing the coupling between Ca2+channels and synaptic vesicles. Thus, we revealed dynamic properties of synaptic vesicles at hMFBs.

    更新日期:2017-11-02
  • DISC1 Regulates Neurogenesis via Modulating Kinetochore Attachment of Ndel1/Nde1 during Mitosis
    Neuron (IF 14.024) Pub Date : 2017-11-02
    Fei Ye, Eunchai Kang, Chuan Yu, Xuyu Qian, Fadi Jacob, Cong Yu, Mao Mao, Randy Y.C. Poon, Jieun Kim, Hongjun Song, Guo-li Ming, Mingjie Zhang

    Mutations ofDISC1(disrupted-in-schizophrenia 1) have been associated with major psychiatric disorders. Despite the hundreds of DISC1-binding proteins reported, almost nothing is known about how DISC1 interacts with other proteins structurally to impact human brain development. Here we solved the high-resolution structure of DISC1 C-terminal tail in complex with its binding domain of Ndel1. Mechanistically, DISC1 regulates Ndel1’s kinetochore attachment, but not its centrosome localization, during mitosis. Functionally, disrupting DISC1/Ndel1 complex formation prolongs mitotic length and interferes with cell-cycle progression in human cells, and it causes cell-cycle deficits of radial glial cells in the embryonic mouse cortex and human forebrain organoids. We also observed similar deficits in organoids derived from schizophrenia patient induced pluripotent stem cells (iPSCs) with aDISC1mutation that disrupts its interaction with Ndel1. Our study uncovers a new mechanism of action for DISC1 based on its structure, and it has implications for how genetic insults may contribute to psychiatric disorders.

    更新日期:2017-11-02
  • A Genetically Defined Circuit for Arousal from Sleep during Hypercapnia
    Neuron (IF 14.024) Pub Date : 2017-11-02
    Satvinder Kaur, Joshua L. Wang, Loris Ferrari, Stephen Thankachan, Daniel Kroeger, Anne Venner, Michael Lazarus, Andrew Wellman, Elda Arrigoni, Patrick M. Fuller, Clifford B. Saper

    The precise neural circuitry that mediates arousal during sleep apnea is not known. We previously found that glutamatergic neurons in the external lateral parabrachial nucleus (PBel) play a critical role in arousal to elevated CO2 or hypoxia. Because many of the PBel neurons that respond to CO2 express calcitonin gene-related peptide (CGRP), we hypothesized that CGRP may provide a molecular identifier of the CO2 arousal circuit. Here, we report that selective chemogenetic and optogenetic activation of PBelCGRPneurons caused wakefulness, whereas optogenetic inhibition of PBelCGRPneurons prevented arousal to CO2, but not to an acoustic tone or shaking. Optogenetic inhibition of PBelCGRPterminals identified a network of forebrain sites under the control of a PBelCGRPswitch that is necessary to arouse animals from hypercapnia. Our findings define a novel cellular target for interventions that may prevent sleep fragmentation and the attendant cardiovascular and cognitive consequences seen in obstructive sleep apnea.

    更新日期:2017-11-02
  • Fibrinogen Activates BMP Signaling in Oligodendrocyte Progenitor Cells and Inhibits Remyelination after Vascular Damage
    Neuron (IF 14.024) Pub Date : 2017-11-02
    Mark A. Petersen, Jae Kyu Ryu, Kae-Jiun Chang, Ainhoa Etxeberria, Sophia Bardehle, Andrew S. Mendiola, Wanjiru Kamau-Devers, Stephen P.J. Fancy, Andrea Thor, Eric A. Bushong, Bernat Baeza-Raja, Catriona A. Syme, Michael D. Wu, Pamela E. Rios Coronado, Anke Meyer-Franke, Stephanie Yahn, Lauriane Pous, Jae K. Lee, Christian Schachtrup, Hans Lassmann, Eric J. Huang, May H. Han, Martina Absinta, Daniel S. Reich, Mark H. Ellisman, David H. Rowitch, Jonah R. Chan, Katerina Akassoglou

    Blood-brain barrier (BBB) disruption alters the composition of the brain microenvironment by allowing blood proteins into the CNS. However, whether blood-derived molecules serve as extrinsic inhibitors of remyelination is unknown. Here we show that the coagulation factor fibrinogen activates the bone morphogenetic protein (BMP) signaling pathway in oligodendrocyte progenitor cells (OPCs) and suppresses remyelination. Fibrinogen induces phosphorylation of Smad 1/5/8 and inhibits OPC differentiation into myelinating oligodendrocytes (OLs) while promoting an astrocytic fatein vitro. Fibrinogen effects are rescued by BMP type I receptor inhibition using dorsomorphin homolog 1 (DMH1) or CRISPR/Cas9 activin A receptor type I (ACVR1) knockout in OPCs. Fibrinogen and the BMP target Id2 are increased in demyelinated multiple sclerosis (MS) lesions. Therapeutic depletion of fibrinogen decreases BMP signaling and enhances remyelinationin vivo. Targeting fibrinogen may be an upstream therapeutic strategy to promote the regenerative potential of CNS progenitors in diseases with remyelination failure.

    更新日期:2017-11-02
  • Local Order within Global Disorder: Synaptic Architecture of Visual Space
    Neuron (IF 14.024) Pub Date : 2017-11-02
    Benjamin Scholl, Daniel E. Wilson, David Fitzpatrick
    更新日期:2017-11-02
  • Kinetics of Releasable Synaptic Vesicles and Their Plastic Changes at Hippocampal Mossy Fiber Synapses
    Neuron (IF 14.024) Pub Date : 2017-11-02
    Mitsuharu Midorikawa, Takeshi Sakaba
    更新日期:2017-11-02
  • DISC1 Regulates Neurogenesis via Modulating Kinetochore Attachment of Ndel1/Nde1 during Mitosis
    Neuron (IF 14.024) Pub Date : 2017-11-02
    Fei Ye, Eunchai Kang, Chuan Yu, Xuyu Qian, Fadi Jacob, Cong Yu, Mao Mao, Randy Y.C. Poon, Jieun Kim, Hongjun Song, Guo-li Ming, Mingjie Zhang
    更新日期:2017-11-02
  • A Genetically Defined Circuit for Arousal from Sleep during Hypercapnia
    Neuron (IF 14.024) Pub Date : 2017-11-02
    Satvinder Kaur, Joshua L. Wang, Loris Ferrari, Stephen Thankachan, Daniel Kroeger, Anne Venner, Michael Lazarus, Andrew Wellman, Elda Arrigoni, Patrick M. Fuller, Clifford B. Saper
    更新日期:2017-11-02
  • Fibrinogen Activates BMP Signaling in Oligodendrocyte Progenitor Cells and Inhibits Remyelination after Vascular Damage
    Neuron (IF 14.024) Pub Date : 2017-11-02
    Mark A. Petersen, Jae Kyu Ryu, Kae-Jiun Chang, Ainhoa Etxeberria, Sophia Bardehle, Andrew S. Mendiola, Wanjiru Kamau-Devers, Stephen P.J. Fancy, Andrea Thor, Eric A. Bushong, Bernat Baeza-Raja, Catriona A. Syme, Michael D. Wu, Pamela E. Rios Coronado, Anke Meyer-Franke, Stephanie Yahn, Lauriane Pous, Jae K. Lee, Christian Schachtrup, Hans Lassmann, Eric J. Huang, May H. Han, Martina Absinta, Daniel S. Reich, Mark H. Ellisman, David H. Rowitch, Jonah R. Chan, Katerina Akassoglou
    更新日期:2017-11-02
  • Establishing Neuronal Polarity with Environmental and Intrinsic Mechanisms
    Neuron (IF 14.024) Pub Date : 2017-11-01
    Shaul Yogev, Kang Shen
    更新日期:2017-11-01
  • Getting mRNA-Containing Ribonucleoprotein Granules Out of a Nuclear Back Door
    Neuron (IF 14.024) Pub Date : 2017-11-01
    Anup Parchure, Mary Munson, Vivian Budnik
    更新日期:2017-11-01
  • Neural Architecture at the Cellular and Molecular Level
    Neuron (IF 14.024) Pub Date : 2017-11-01

    The striking diversity of cells in the nervous system has long inspired scientists to ask how the various cell types of the nervous system are generated, wired, and respond to each other to allow for the diverse and dynamic behaviors generated by the brain. Neuronal cell biology has been a cornerstone of Neuron since its inception in 1988 and was the focus of a previous special issue in 2003. Just as systems and cognitive neuroscience is flourishing with new technologies to manipulate and visualize neural circuits, molecular and cellular neuroscience is in a time of growth and rapid discovery. Neuroscientists now have technologies at the ready that allow for the ability to detect, quantify, and disrupt cellular and molecular processes with unprecedented temporal and spatial precision. The goal of this special issue is to showcase to the neuroscience community the latest discoveries and ideas in neuronal cell biology and spotlight the importance of understanding the cellular and molecular underpinnings of nervous system architecture and function. In addition, we also want to capture the attention of “traditional” cell biologists (from outside of neuroscience) and inspire them to think about the unique challenges the nervous system presents for cell biology and perhaps even get them to deploy their talents and expertise in this direction. Much in the way that chemists, physicists, and theoreticians have galvanized neuroscience over the last decade, we see great potential for the field in bringing more cell biologists and cell biological approaches into the neuroscience fold.

    更新日期:2017-11-01
  • Compartmentalized Signaling in Neurons: From Cell Biology to Neuroscience
    Neuron (IF 14.024) Pub Date : 2017-11-01
    Marco Terenzio, Giampietro Schiavo, Mike Fainzilber
    更新日期:2017-11-01
  • The BRAIN Initiative Cell Census Consortium: Lessons Learned toward Generating a Comprehensive Brain Cell Atlas
    Neuron (IF 14.024) Pub Date : 2017-11-01
    Joseph R. Ecker, Daniel H. Geschwind, Arnold R. Kriegstein, John Ngai, Pavel Osten, Damon Polioudakis, Aviv Regev, Nenad Sestan, Ian R. Wickersham, Hongkui Zeng

    A comprehensive characterization of neuronal cell types, their distributions, and patterns of connectivity is critical for understanding the properties of neural circuits and how they generate behaviors. Here we review the experiences of the BRAIN Initiative Cell Census Consortium, ten pilot projects funded by the U.S. BRAIN Initiative, in developing, validating, and scaling up emerging genomic and anatomical mapping technologies for creating a complete inventory of neuronal cell types and their connections in multiple species and during development. These projects lay the foundation for a larger and longer-term effort to generate whole-brain cell atlases in species including mice and humans.

    更新日期:2017-11-01
  • Transcellular Nanoalignment of Synaptic Function
    Neuron (IF 14.024) Pub Date : 2017-11-01
    Thomas Biederer, Pascal S. Kaeser, Thomas A. Blanpied
    更新日期:2017-11-01
  • Molecular Neuroscience in the 21st Century: A Personal Perspective
    Neuron (IF 14.024) Pub Date : 2017-11-01
    Thomas C. Südhof
    更新日期:2017-11-01
  • Regulation of mRNA Translation in Neurons—A Matter of Life and Death
    Neuron (IF 14.024) Pub Date : 2017-11-01
    Mridu Kapur, Caitlin E. Monaghan, Susan L. Ackerman
    更新日期:2017-11-01
  • Cell Biology of Astrocyte-Synapse Interactions
    Neuron (IF 14.024) Pub Date : 2017-11-01
    Nicola J. Allen, Cagla Eroglu
    更新日期:2017-11-01
  • Mitostasis in Neurons: Maintaining Mitochondria in an Extended Cellular Architecture
    Neuron (IF 14.024) Pub Date : 2017-11-01
    Thomas Misgeld, Thomas L. Schwarz
    更新日期:2017-11-01
  • Optogenetic Tools for Subcellular Applications in Neuroscience
    Neuron (IF 14.024) Pub Date : 2017-11-01
    Benjamin R. Rost, Franziska Schneider-Warme, Dietmar Schmitz, Peter Hegemann
    更新日期:2017-11-01
  • A Primer on Concepts and Applications of Proteomics in Neuroscience
    Neuron (IF 14.024) Pub Date : 2017-11-01
    Fabian Hosp, Matthias Mann
    更新日期:2017-11-01
  • Entrainment of Arteriole Vasomotor Fluctuations by Neural Activity Is a Basis of Blood-Oxygenation-Level-Dependent “Resting-State” Connectivity
    Neuron (IF 14.024) Pub Date : 2017-10-26
    Celine Mateo, Per M. Knutsen, Philbert S. Tsai, Andy Y. Shih, David Kleinfeld

    Resting-state signals in blood-oxygenation-level-dependent (BOLD) imaging are used to parcellate brain regions and define “functional connections” between regions. Yet a physiological link between fluctuations in blood oxygenation with those in neuronal signaling pathways is missing. We present evidence from studies on mouse cortex that modulation of vasomotion, i.e., intrinsic ultra-slow (0.1 Hz) fluctuations in arteriole diameter, provides this link. First, ultra-slow fluctuations in neuronal signaling, which occur as an envelope over γ-band activity, entrains vasomotion. Second, optogenetic manipulations confirm that entrainment is unidirectional. Third, co-fluctuations in the diameter of pairs of arterioles within the same hemisphere diminish to chance for separations >1.4 mm. Yet the diameters of arterioles in distant (>5 mm), mirrored transhemispheric sites strongly co-fluctuate; these correlations are diminished in acallosal mice. Fourth, fluctuations in arteriole diameter coherently drive fluctuations in blood oxygenation. Thus, entrainment of vasomotion links neuronal pathways to functional connections.

    更新日期:2017-10-27
  • Transsynaptic Mapping of Second-Order Taste Neurons in Flies by trans-Tango
    Neuron (IF 14.024) Pub Date : 2017-10-26
    Mustafa Talay, Ethan B. Richman, Nathaniel J. Snell, Griffin G. Hartmann, John D. Fisher, Altar Sorkaç, Juan F. Santoyo, Cambria Chou-Freed, Nived Nair, Mark Johnson, John R. Szymanski, Gilad Barnea

    Mapping neural circuits across defined synapses is essential for understanding brain function. Here we describetrans-Tango, a technique for anterograde transsynaptic circuit tracing and manipulation. At the core oftrans-Tango is a synthetic signaling pathway that is introduced into all neurons in the animal. This pathway converts receptor activation at the cell surface into reporter expression through site-specific proteolysis. Specific labeling is achieved by presenting a tethered ligand at the synapses of genetically defined neurons, thereby activating the pathway in their postsynaptic partners and providing genetic access to these neurons. We first validatedtrans-Tango in theDrosophilaolfactory system and then implemented it in the gustatory system, where projections beyond the first-order receptor neurons are not fully characterized. We identified putative second-order neurons within the sweet circuit that include projection neurons targeting known neuromodulation centers in the brain. These experiments establishtrans-Tango as a flexible platform for transsynaptic circuit analysis.

    更新日期:2017-10-27
  • Molecular Dissection of Neuroligin 2 and Slitrk3 Reveals an Essential Framework for GABAergic Synapse Development
    Neuron (IF 14.024) Pub Date : 2017-10-26
    Jun Li, Wenyan Han, Kenneth A. Pelkey, Jingjing Duan, Xia Mao, Ya-Xian Wang, Michael T. Craig, Lijin Dong, Ronald S. Petralia, Chris J. McBain, Wei Lu

    In the brain, many types of interneurons make functionally diverse inhibitory synapses onto principal neurons. Although numerous molecules have been identified to function in inhibitory synapse development, it remains unknown whether there is a unifying mechanism for development of diverse inhibitory synapses. Here we report a general molecular mechanism underlying hippocampal inhibitory synapse development. In developing neurons, the establishment of GABAergic transmission depends on Neuroligin 2 (NL2), a synaptic cell adhesion molecule (CAM). During maturation, inhibitory synapse development requires both NL2 and Slitrk3 (ST3), another CAM. Importantly, NL2 and ST3 interact with nanomolar affinity through their extracellular domains to synergistically promote synapse development. Selective perturbation of the NL2-ST3 interaction impairs inhibitory synapse development with consequent disruptions in hippocampal network activity and increased seizure susceptibility. Our findings reveal how unique postsynaptic CAMs work in concert to control synaptogenesis and establish a general framework for GABAergic synapse development.

    更新日期:2017-10-27
  • “Silent” NMDA Synapses Enhance Motion Sensitivity in a Mature Retinal Circuit
    Neuron (IF 14.024) Pub Date : 2017-10-26
    Santhosh Sethuramanujam, Xiaoyang Yao, Geoff deRosenroll, Kevin L. Briggman, Greg D. Field, Gautam B. Awatramani

    Retinal direction-selective ganglion cells (DSGCs) have the remarkable ability to encode motion over a wide range of contrasts, relying on well-coordinated excitation and inhibition (E/I). E/I is orchestrated by a diverse set of glutamatergic bipolar cells that drive DSGCs directly, as well as indirectly through feedforward GABAergic/cholinergic signals mediated by starburst amacrine cells. Determining how direction-selective responses are generated across varied stimulus conditions requires understanding how glutamate, acetylcholine, and GABA signals are precisely coordinated. Here, we use a combination of paired patch-clamp recordings, serial EM, and large-scale multi-electrode array recordings to show that a single high-sensitivity source of glutamate is processed differentially by starbursts via AMPA receptors and DSGCs via NMDA receptors. We further demonstrate how this novel synaptic arrangement enables DSGCs to encode direction robustly near threshold contrasts. Together, these results reveal a space-efficient synaptic circuit model for direction computations, in which “silent” NMDA receptors play critical roles.

    更新日期:2017-10-27
  • Deprivation-Induced Homeostatic Spine Scaling In Vivo Is Localized to Dendritic Branches that Have Undergone Recent Spine Loss
    Neuron (IF 14.024) Pub Date : 2017-10-26
    Samuel J. Barnes, Eleonora Franzoni, R. Irene Jacobsen, Ferenc Erdelyi, Gabor Szabo, Claudia Clopath, Georg B. Keller, Tara Keck

    Synaptic scaling is a key homeostatic plasticity mechanism and is thought to be involved in the regulation of cortical activity levels. Here we investigated the spatial scale of homeostatic changes in spine size following sensory deprivation in a subset of inhibitory (layer 2/3GAD65-positive) and excitatory (layer 5Thy1-positive) neurons in mouse visual cortex. Using repeatedin vivotwo-photon imaging, we find that increases in spine size are tumor necrosis factor alpha (TNF-α) dependent and thus are likely associated with synaptic scaling. Rather than occurring at all spines, the observed increases in spine size are spatially localized to a subset of dendritic branches and are correlated with the degree of recent local spine loss within that branch. Using simulations, we show that such a compartmentalized form of synaptic scaling has computational benefits over cell-wide scaling for information processing within the cell.

    更新日期:2017-10-27
  • Direct Dopaminergic Projections from the SNc Modulate Visuomotor Transformation in the Lamprey Tectum
    Neuron (IF 14.024) Pub Date : 2017-10-26
    Juan Pérez-Fernández, Andreas A. Kardamakis, Daichi G. Suzuki, Brita Robertson, Sten Grillner

    Dopamine neurons in the SNc play a pivotal role in modulating motor behavior via striatum. Here, we show that the same dopamine neuron that targets striatum also sends a direct branch to the optic tectum (superior colliculus). Whenever SNc neurons are activated, both targets will therefore be affected. Visual stimuli (looming or bars) activate the dopamine neurons coding saliency and also elicit distinct motor responses mediated via tectum (eye, orienting or evasive), which are modulated by the dopamine input. Whole-cell recordings from tectal projection neurons and interneurons show that dopamine, released by SNc stimulation, increases or decreases the excitability depending on whether they express the dopamine D1 or the D2 receptor. SNc thus exerts its effects on the visuomotor system through a combined effect directly on tectum and also via striatum. This direct SNc modulation will occur regardless of striatum and represents a novel mode of motor control.

    更新日期:2017-10-27
  • A Large-Scale Semi-Chronic Microdrive Recording System for Non-Human Primates
    Neuron (IF 14.024) Pub Date : 2017-10-26
    Nicholas M. Dotson, Steven J. Hoffman, Baldwin Goodell, Charles M. Gray

    Multi-electrode recordings in the non-human primate provide a critical method for measuring the widely distributed activity patterns that underlie brain function. However, common techniques rely on small, often immovable arrays, or microdrives, that are only capable of manipulating a small number of closely spaced probes. These techniques restrict the number of cortical areas that can be simultaneously sampled and are typically not capable of reaching subcortical targets. To overcome these limitations, we developed a large-scale, semi-chronic microdrive recording system with up to 256 independently movable microelectrodes spanning an entire cerebral hemisphere. The microdrive system is hermetically sealed, free of internal connecting wires, and has been used to simultaneously record from up to 37 cortical and subcortical areas in awake behaving monkeys for up to 9 months. As a proof of principle, we demonstrate the capability of this technique to address network-level questions using a graph theoretic analysis of functional connectivity data.

    更新日期:2017-10-27
  • Entrainment of Arteriole Vasomotor Fluctuations by Neural Activity Is a Basis of Blood-Oxygenation-Level-Dependent “Resting-State” Connectivity
    Neuron (IF 14.024) Pub Date : 2017-10-26
    Celine Mateo, Per M. Knutsen, Philbert S. Tsai, Andy Y. Shih, David Kleinfeld
    更新日期:2017-10-27
  • Transsynaptic Mapping of Second-Order Taste Neurons in Flies by trans-Tango
    Neuron (IF 14.024) Pub Date : 2017-10-26
    Mustafa Talay, Ethan B. Richman, Nathaniel J. Snell, Griffin G. Hartmann, John D. Fisher, Altar Sorkaç, Juan F. Santoyo, Cambria Chou-Freed, Nived Nair, Mark Johnson, John R. Szymanski, Gilad Barnea
    更新日期:2017-10-27
  • Molecular Dissection of Neuroligin 2 and Slitrk3 Reveals an Essential Framework for GABAergic Synapse Development
    Neuron (IF 14.024) Pub Date : 2017-10-26
    Jun Li, Wenyan Han, Kenneth A. Pelkey, Jingjing Duan, Xia Mao, Ya-Xian Wang, Michael T. Craig, Lijin Dong, Ronald S. Petralia, Chris J. McBain, Wei Lu
    更新日期:2017-10-27
  • “Silent” NMDA Synapses Enhance Motion Sensitivity in a Mature Retinal Circuit
    Neuron (IF 14.024) Pub Date : 2017-10-26
    Santhosh Sethuramanujam, Xiaoyang Yao, Geoff deRosenroll, Kevin L. Briggman, Greg D. Field, Gautam B. Awatramani
    更新日期:2017-10-27
  • Deprivation-Induced Homeostatic Spine Scaling In Vivo Is Localized to Dendritic Branches that Have Undergone Recent Spine Loss
    Neuron (IF 14.024) Pub Date : 2017-10-26
    Samuel J. Barnes, Eleonora Franzoni, R. Irene Jacobsen, Ferenc Erdelyi, Gabor Szabo, Claudia Clopath, Georg B. Keller, Tara Keck
    更新日期:2017-10-27
  • Direct Dopaminergic Projections from the SNc Modulate Visuomotor Transformation in the Lamprey Tectum
    Neuron (IF 14.024) Pub Date : 2017-10-26
    Juan Pérez-Fernández, Andreas A. Kardamakis, Daichi G. Suzuki, Brita Robertson, Sten Grillner
    更新日期:2017-10-27
  • A Large-Scale Semi-Chronic Microdrive Recording System for Non-Human Primates
    Neuron (IF 14.024) Pub Date : 2017-10-26
    Nicholas M. Dotson, Steven J. Hoffman, Baldwin Goodell, Charles M. Gray
    更新日期:2017-10-27
  • Virus-Mediated Genome Editing via Homology-Directed Repair in Mitotic and Postmitotic Cells in Mammalian Brain
    Neuron (IF 14.024) Pub Date : 2017-10-19
    Jun Nishiyama, Takayasu Mikuni, Ryohei Yasuda

    Precise genome editing via homology-directed repair (HDR) in targeted cells, particularlyin vivo, provides an invaluable tool for biomedical research. However, HDR has been considered to be largely restricted to dividing cells, making it challenging to apply the technique in postmitotic neurons. Here we show that precise genome editing via HDR is possible in mature postmitotic neurons as well as mitotic cells in mice brain by combining CRISPR-Cas9-mediated DNA cleavage and the efficient delivery of donor template with adeno-associated virus (AAV). Using this strategy, we achieved efficient tagging of endogenous proteins in primary and organotypic culturesin vitroand developing, adult, aged, and pathological brainsin vivo. Thus, AAV- and CRISPR-Cas9-mediated HDR will be broadly useful for precise genome editing in basic and translational neuroscience.

    更新日期:2017-10-19
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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