Neuron: March 6, 2019 (Volume 101, Issue 5)

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[Click here to register and submit your abstract.](%2F%2Fwww.cell-symposia.com%2Fneuroimmunology-2019%2F/2/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/gpWim7GsLZOimYeGp09w8CBuIzw=99) [Check out the latest jobs in the life sciences on the Cell Career Network](%2F%2Fcareers.cell.com%2F/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/8VW9Ph_h9JqcTWrK0L3BcZ9OfP4=99) Special Issue on Translational Neuroscience --------------------------------------------------------------- [Special Issue on Disease: Translational Approaches](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30155-2/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/hApWCUTfnHAuh0iWYCYi66Zwl_0=99) Christina Konen, Emily Niederst [Ketamine: A Paradigm Shift for Depression Research and Treatment (Featured)](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30114-X/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/-3zUEacj-gVYtrUZdmKbDCBOexc=99) John H. Krystal, Chadi G. Abdallah, Gerard Sanacora, Dennis S. Charney, Ronald S. Duman [Advancing Translational Research Using NIMH Research Domain Criteria and Computational Methods (Featured)](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30159-X/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/6I434d1MBtXqbpBYHhABeemRadM=99) Charles A. Sanislow, Michele Ferrante, Jennifer Pacheco, Matthew V. Rudorfer, Sarah E. Morris [Composite Pain Biomarker Signatures for Objective Assessment and Effective Treatment](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30154-0/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/_DkEAjlk5hH98XoVbJJ3r-EDmJ8=99) Irene Tracey, Clifford J. Woolf, Nick A. Andrews [Huntingtin Lowering Strategies for Disease Modification in Huntington’s Disease](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30066-2/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/9QmrzaVbfdYIVl52jzWIlkBqgZ4=99) Sarah J. Tabrizi, Rhia Ghosh, Blair R. Leavitt [A Quarter Century of APOE and Alzheimer’s Disease: Progress to Date and the Path Forward (Featured)](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30083-2/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/q4fXDfwpqU237oE5gj5mKcu-ICE=99) Michaël E. Belloy, Valerio Napolioni, Michael D. Greicius [Therapeutic AAV Gene Transfer to the Nervous System: A Clinical Reality (Featured)](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30126-6/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/g6qaS0Wnr-SEnXc8LaBymPYZWHE=99) Eloise Hudry, Luk H. Vandenberghe Online Now --------------------------------------------------------------- [Higher-Order Thalamic Circuits Channel Parallel Streams of Visual Information in Mice](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30119-9/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/sXDInrQrUfNMxp5069ECMoi9DDg=99) Bennett et al. [ARNT2 Tunes Activity-Dependent Gene Expression through NCoR2-Mediated Repression and NPAS4-Mediated Activation](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30116-3/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/sfbb8-WujXCGytBOzCWfwCb5skk=99) Sharma et al. Video Abstract --------------------------------------------------------------- %2F%2Fwww.youtube.com%2Fwatch%3Ftime_continue=1%26v=83XBZS8Y-rU/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/oEayEX5rINmlIKkwBwNw_hkFUQo=99 [A New Tool for Controlling Synapse Function with Light](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30003-0/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/9QwAYbiX-tX_3nCsa_LIuDLCg4Q=99) This video abstract highlights a recent collaborative project between labs at the University of Colorado, School of Medicine, and Goethe University, Frankfurt. Liu et al. describe how they engineered and validated a light-activated neurotoxin that allows users to switch off synapses with spatial and temporal control. %2F%2Fwww.youtube.com%2Fwatch%3Fv=vqfmd9e2gqc/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/9J2AsOWTAN32QSnGmA8XkEI-dF4=99 [Defining the Functional Role of NaV1.7 in Human Nociception](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30074-1/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/zJ3jGCwwtub8G_DoDwYD1wQ8ZgY=99) Gene mutations associated with painless phenotypes offer great insight for analgesic development. Using a multi-modal approach, McDermott et al. show that mutations in the voltage-gated sodium channel NaV1.7 cause congenital insensitivity to pain due to a lack of functional nociceptors. Some cartoons were made using items from the Servier Medical Art Powerpoint Image Bank under their Creative Commons Attribution License. Table of Contents Previews --------------------------------------------------------------- [The Excitatory, the Inhibitory, and the Modulatory: Mapping Chemical Neurotransmission in the Brain](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30156-4%3Fdgcid=raven_jbs_etoc_email/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/0eK6KALTVEHy2BZWohrU8pHdFII=99) Tamara Boto, Seth M. Tomchik In this issue of Neuron, Deng et al. (2019) report the generation of a new set of tools to manipulate the entire set of neurotransmitters, neuromodulators, neuropeptides, and their receptors—the “chemoconnectome”—in Drosophila. [The Two Sides of NaV1.7: Painful and Painless Channelopathies](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30125-4%3Fdgcid=raven_jbs_etoc_email/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/VfH6CPkxv6hNiVT4tE1LJKPk2rM=99) Stephen G. Waxman, Sulayman D. Dib-Hajj Sodium channel NaV1.7 is a major target in pain research, largely because of genetic validation. In this issue of Neuron, McDermott et al. (2019) now present a comprehensive assessment of congenital pain insensitivity due to NaV1.7 loss of function. This work and studies on NaV1.7 gain of function raise important questions about how channelopathies produce disease. [Order in Odors: A Power Law Structures the Encoding of Stimulus Identity and Intensity](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30157-6%3Fdgcid=raven_jbs_etoc_email/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/hYmeJdJ8J5LNNQ8MLTA_KByheN8=99) Matthieu Louis Odorant molecules are detected through the combinatorial activation of ensembles of olfactory sensory neurons. By capitalizing on the numerical simplicity of the Drosophila larval brain, Si et al. (2019) uncover principles constraining the representation of the quality and intensity of olfactory stimuli. [Looking into the Brain of Buridan’s Ass](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30160-6%3Fdgcid=raven_jbs_etoc_email/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/cOjnsI_qxSq9QONq-QJDHWaja9o=99) Mathias Pessiglione, Nicolas Clairis To survive, animals must maximize the minimum—take care of the least satisfied among their basic needs. In this issue of Neuron, a study by Juechems et al. (2019) illustrates that this core principle might shape the way medial prefrontal regions of the human brain drive and valuate sequential choices between different types of reward. Editorial --------------------------------------------------------------- [Special Issue on Disease: Translational Approaches](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30155-2%3Fdgcid=raven_jbs_etoc_email/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/TkvKoeULTLney0__r8aYHLeMhD0=99) Christina Konen, Emily Niederst NeuroViews --------------------------------------------------------------- [Ketamine: A Paradigm Shift for Depression Research and Treatment](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30114-X%3Fdgcid=raven_jbs_etoc_email/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/r4-drSkP6lKT4-Sx_SVbwJ8dEnc=99) John H. Krystal, Chadi G. Abdallah, Gerard Sanacora, Dennis S. Charney, Ronald S. Duman Ketamine is the first exemplar of a rapid-acting antidepressant with efficacy for treatment-resistant symptoms of mood disorders. Its discovery emerged from a reconceptualization of the biology of depression. Neurobiological insights into ketamine efficacy shed new light on the mechanisms underlying antidepressant efficacy. [Advancing Translational Research Using NIMH Research Domain Criteria and Computational Methods](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30159-X%3Fdgcid=raven_jbs_etoc_email/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/n0NJfXwXntcmBx8vcT52o1MkxBM=99) Charles A. Sanislow, Michele Ferrante, Jennifer Pacheco, Matthew V. Rudorfer, Sarah E. Morris NIMH’s Research Domain Criteria is a framework for dimensional, trans-diagnostic research on mental disorders. Sanislow et al. discuss ways in which research leveraging computational methods can identify intermediary treatment targets and accelerate translational progress. Perspective --------------------------------------------------------------- [Composite Pain Biomarker Signatures for Objective Assessment and Effective Treatment](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30154-0%3Fdgcid=raven_jbs_etoc_email/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/NZ8v7jfx2T9-PPHT5ykaPrqLNpU=99) Irene Tracey, Clifford J. Woolf, Nick A. Andrews This Perspective highlights the significance of chronic pain, its underpinning biology, and the need for composite biomarker signatures alongside self-report. Combining evidence from animal and human research spanning genetics through to neuroimaging, Tracey et al. highlight a few key areas of promise. Reviews --------------------------------------------------------------- [Huntingtin Lowering Strategies for Disease Modification in Huntington’s Disease](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30066-2%3Fdgcid=raven_jbs_etoc_email/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/uWydy93UsSLJZIS47EVA5g5regg=99) Sarah J. Tabrizi, Rhia Ghosh, Blair R. Leavitt In this review, Tabrizi et al. describe new approaches to disease modification in Huntington’s disease. These aim to reduce mutant huntingtin protein by targeting huntingtin DNA, RNA, and the mutant protein itself, in theory ameliorating all of its downstream pathogenic effects. [A Quarter Century of APOE and Alzheimer’s Disease: Progress to Date and the Path Forward](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30083-2%3Fdgcid=raven_jbs_etoc_email/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/Jg_TVvRVQz2m5yHi7Wx3IcgQUTs=99) Michaël E. Belloy, Valerio Napolioni, Michael D. Greicius Does APOE4 increase risk for Alzheimer’s disease via a gain or loss of function? Belloy et al., focusing on human data, examine critical issues like pleiotropy, sex, and ancestral background, to address this fundamental question. [Therapeutic AAV Gene Transfer to the Nervous System: A Clinical Reality](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30126-6%3Fdgcid=raven_jbs_etoc_email/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/FZxqXzWvhVRgzSlAX64utRT_vgk=99) Eloise Hudry, Luk H. Vandenberghe Conceptually intuitive, however complex in execution, gene therapy is emerging as a therapeutic modality that can have a transformative impact on patients’ lives. Hudry and Vandenberghe review the clinical progress in gene therapy for nervous system disorders using AAV. NeuroResources --------------------------------------------------------------- [A Photoactivatable Botulinum Neurotoxin for Inducible Control of Neurotransmission](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30003-0%3Fdgcid=raven_jbs_etoc_email/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/8oXczBU2miJ_Cp6KO43_PPSylww=99) Qi Liu, Brooke L. Sinnen, Emma E. Boxer, Martin W. Schneider, Michael J. Grybko, William C. Buchta, Emily S. Gibson, Christina L. Wysoczynski, Christopher P. Ford, Alexander Gottschalk, Jason Aoto, Chandra L. Tucker, Matthew J. Kennedy Few tools in neuroscience allow long-term synapse inhibition with light. We engineered botulinum neurotoxin B so that it can be switched on with blue light. Light activation results in robust proteolysis of VAMP2, a SNARE protein universally required for neurotransmitter release. [Chemoconnectomics: Mapping Chemical Transmission in Drosophila](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30072-8%3Fdgcid=raven_jbs_etoc_email/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/y5xy5G58JJ0s3TAZrMnbDQ6r_us=99) Bowen Deng, Qi Li, Xinxing Liu, Yue Cao, Bingfeng Li, Yongjun Qian, Rui Xu, Renbo Mao, Enxing Zhou, Wenxia Zhang, Juan Huang, Yi Rao Deng et al. propose the concept of the chemoconnectome (CCT) as the entirety of all neurotransmitters, neuromodulators, neuropeptides, and their receptors and the approach of chemoconnectomics to trace neural circuitry anatomically and functionally. Report --------------------------------------------------------------- [Cell-type-Specific Patterned Stimulus-Independent Neuronal Activity in the Drosophila Visual System during Synapse Formation](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30009-1%3Fdgcid=raven_jbs_etoc_email/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/8arweMkp8sZkBY0u2X0V8zeEJgw=99) Orkun Akin, Bryce T. Bajar, Mehmet F. Keles, Mark A. Frye, S. Lawrence Zipursky Akin and Bajar et al. report that stimulus-independent neural activity occurs in cell-type-specific patterns during synapse formation in Drosophila. Their findings suggest that neural activity may be a fundamental feature of brain development. Articles --------------------------------------------------------------- [Defining the Functional Role of NaV1.7 in Human Nociception](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30074-1%3Fdgcid=raven_jbs_etoc_email/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/ploP27kB5SeQC2leeIEfwyF2Aug=99) Lucy A. McDermott, Greg A. Weir, Andreas C. Themistocleous, Andrew R. Segerdahl, Iulia Blesneac, Georgios Baskozos, Alex J. Clark, Val Millar, Liam J. Peck, Daniel Ebner, Irene Tracey, Jordi Serra, David L. Bennett Open Access Gene mutations associated with painless phenotypes offer great insight for analgesic development. Using a multi-modal approach, McDermott et al. show that mutations in the voltage-gated sodium channel NaV1.7 cause congenital insensitivity to pain due to a lack of functional nociceptors. [Endothelium-Derived Semaphorin 3G Regulates Hippocampal Synaptic Structure and Plasticity via Neuropilin-2/PlexinA4](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)31156-5%3Fdgcid=raven_jbs_etoc_email/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/sYnci86FmVZ9lKZ5QGwFY00IcxQ=99) Chao Tan, Nan-Nan Lu, Cheng-Kun Wang, Dan-Yang Chen, Ning-He Sun, Hang Lyu, Jakob Körbelin, Wei-Xing Shi, Kohji Fukunaga, Ying-Mei Lu, Feng Han Tan et al. reveal a key mechanism that underlies signaling from endothelial cells to neurons in the brain. They identify that the endothelium-secreted protein semaphorin 3G (Sema3G) regulates synaptic structure and plasticity in hippocampal neurons through its neuronal neuropilin-2/PlexinA4 holoreceptor. [Neuronal Regulation of Fast Synaptotagmin Isoforms Controls the Relative Contributions of Synchronous and Asynchronous Release](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30014-5%3Fdgcid=raven_jbs_etoc_email/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/HvEJBY_pUkKCZJtpwTe-jych408=99) Josef Turecek, Wade G. Regehr The synchrony of GABA release in the inferior olive is regionally specialized. We find that Syt7 controls the kinetics of asynchronous release and that release synchrony is controlled by the presence or absence of fast Syt isoforms. [Structured Odorant Response Patterns across a Complete Olfactory Receptor Neuron Population](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)31150-4%3Fdgcid=raven_jbs_etoc_email/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/06v7Hi397Wn7RFNaVHV7NvFhusY=99) Guangwei Si, Jessleen K. Kanwal, Yu Hu, Christopher J. Tabone, Jacob Baron, Matthew Berck, Gaetan Vignoud, Aravinthan D.T. Samuel The combinatorial olfactory code conveys odor stimulus features in an entangled manner. Si et al. uncover structure and statistical properties in ORN responses that allow separated representations of odor features and shine light on the mechanism of molecular recognition by olfactory receptors. [Activity Correlations between Direction-Selective Retinal Ganglion Cells Synergistically Enhance Motion Decoding from Complex Visual Scenes](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30004-2%3Fdgcid=raven_jbs_etoc_email/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/RRCgfoChiaj554l68AH7M1n77XE=99) Norma Krystyna Kühn, Tim Gollisch Open Access Direction-selective retinal ganglion cells encode visual motion but also respond to luminance changes. Kühn and Gollisch report that this dual-feature sensitivity creates ambiguities for decoding complex motion stimuli. Population decoding resolves these ambiguities and provides a synergistic motion readout. [A Network for Computing Value Equilibrium in the Human Medial Prefrontal Cortex](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)31149-8%3Fdgcid=raven_jbs_etoc_email/1/01000169544c5523-ef412ac3-e86f-40cf-adbb-813efca9af88-000000/7-j985enNCTS3ES6YgkqvEXZZ68=99) Keno Juechems, Jan Balaguer, Santiago Herce Castañón, María Ruz, Jill X. O’Reilly, Christopher Summerfield Humans often need to maintain equilibrium between competing goals. Juechems et al. show that a region in the rostral ACC monitors this equilibrium, whereas the vmPFC encodes the redress in imbalance between goals incurred by choice. 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