Neuron: November 16, 2022 (Volume 110, Issue 22)

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Featured articles --------------------------------------------------------------- [Next-generation brain observatories](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00899-6/1/01000184814be300-5324a5d9-5c18-4a93-afae-e83f820237fe-000000/UncIUy_xsjgIBUeh0HPPZUzA90TA9mEcmhuqNYT2Zds=275) Koch et al. [Multiscale imaging informs translational mouse modeling of neurological disease](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00811-X/1/01000184814be300-5324a5d9-5c18-4a93-afae-e83f820237fe-000000/rIie1VH7Z008uIlPW_8QF-MqPM45WHjZj4rq4JBBxTQ=275) Wang et al. [Sensing sound: Cellular specializations and molecular force sensors](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00857-1/1/01000184814be300-5324a5d9-5c18-4a93-afae-e83f820237fe-000000/QuQEzpY04BYipRl8uw2ZuPwaHFkQxVIo6_OlW69x6nk=275) Qui et al. [Prefrontal-habenular microstructural impairments in human cocaine and heroin addiction](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00816-9/1/01000184814be300-5324a5d9-5c18-4a93-afae-e83f820237fe-000000/LxfhsvN22QpGs7Sbbx5YFEkz41WsMjTI8X_UFkb8m_k=275) King et al Online now --------------------------------------------------------------- [Dually innervated dendritic spines develop in the absence of excitatory activity and resist plasticity through tonic inhibitory crosstalk](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)01001-7/1/01000184814be300-5324a5d9-5c18-4a93-afae-e83f820237fe-000000/iXUNTC7BvWP5BHotLDFmqWYOmOdrenMW31lNeTHwoUo=275) Kleinjan et al. [Astrocyte endfoot formation controls the termination of oligodendrocyte precursor cell perivascular migration during development](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00991-6/1/01000184814be300-5324a5d9-5c18-4a93-afae-e83f820237fe-000000/1dLkUufEgQQcyoYuEcIWPmrbTL0kOhJ7DZkFvu3E-24=275) Su et al. [Cortical VIP neurons locally control the gain but globally control the coherence of gamma band rhythms](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00996-5/1/01000184814be300-5324a5d9-5c18-4a93-afae-e83f820237fe-000000/VuFcZowO7k0LWbgM9nXDETHoMAwAvVGY7Q2ERiqZuXM=275) Veit et al. [The miR-124-AMPAR pathway connects polygenic risks with behavioral changes shared between schizophrenia and bipolar disorder](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00964-3/1/01000184814be300-5324a5d9-5c18-4a93-afae-e83f820237fe-000000/nHXjp-m9dFwmSFEWYn5GXV3cHGCxFW7lavoJDSk9QKY=275) Namkung et al. Table of Contents Previews --------------------------------------------------------------- [Homing in on homeostatic plasticity](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00993-X%3Fdgcid=raven_jbs_etoc_email/1/01000184814be300-5324a5d9-5c18-4a93-afae-e83f820237fe-000000/68hsv3akEztztOW80hKMPMmQ3gb0yEfjd1xeJuaohOk=275) Ruud F. Toonen, Matthijs Verhage In this issue of Neuron, Orr et al.1 demonstrate a detailed molecular cascade that drives presynaptic homeostatic plasticity and enhances presynaptic vesicle fusion in response to reduced postsynaptic activity. Two large presynaptic signaling complexes are central hubs. [The perfect timing for multimodal integration is not the same in all L5 neurons](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00902-3%3Fdgcid=raven_jbs_etoc_email/1/01000184814be300-5324a5d9-5c18-4a93-afae-e83f820237fe-000000/vqcLHyjjJ7cVTRCm4U2t92M-G-8RzRVcwhubSj-kRDw=275) Flora Vasile, Leopoldo Petreanu In this issue of Neuron, Rindner et al. (2022) demonstrate that subclasses of layer 5 pyramidal neurons in the parietal cortex integrate inputs from frontal and sensory areas supralinearly and with distinct temporal dynamics. [Genetically tagging cholinergic diversity](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00913-8%3Fdgcid=raven_jbs_etoc_email/1/01000184814be300-5324a5d9-5c18-4a93-afae-e83f820237fe-000000/MIelv0Gb68BPtDARtf4VHicB30dohFnHbcsc82WsBJ0=275) Jiaqi Keith Luo, Lucas Pinto In this issue of Neuron, Li et al. (2022) identify and genetically target two sub-populations of cholinergic neurons in the basal forebrain. They show that these cholinergic subtypes have distinct projection patterns, electrophysiological phenotypes, and behavioral functions. [Dopamine in the rodent tail of striatum regulates behavioral variability in response to threatening novel objects](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00952-7%3Fdgcid=raven_jbs_etoc_email/1/01000184814be300-5324a5d9-5c18-4a93-afae-e83f820237fe-000000/AWTODLGhwGZ_d1X-I72PyQrS9-zRbsbeKN8Gr-CSSQQ=275) Julia Pai, Ilya E. Monosov Mice display variability in fear-like responses to many external salient events, such as encountering unexpected novel objects, but the neural basis of this variability has been unclear. Akiti et al. (2022) demonstrate that dopamine in the tail of the rodent striatum predicts and regulates salience-related variability in individuals’ behavioral responses to unexpected novel objects. Meeting report --------------------------------------------------------------- [Molecular neuroscience community shares perspectives](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00962-X%3Fdgcid=raven_jbs_etoc_email/1/01000184814be300-5324a5d9-5c18-4a93-afae-e83f820237fe-000000/peZL-StK06KgNVQLKT9KiIGK6YcxLotCrA_6t3_7AOE=275) Trisha Gura, Amparo Acker-Palmer, Alex Kolodkin, Rob Meijers, Naoko Mizuno, Elena Seiradake, Marc Tessier-Lavigne In May, an interdisciplinary group gathered in Crete for the Molecular Neurobiology Workshop. Scientists shared data acquired by vastly diverse techniques to understand how the nervous system, with only a limited number of components, is assembled to respond to infinite stimuli. Ideas of molecular cues, timing, switching, and context emerged. NeuroView --------------------------------------------------------------- [Next-generation brain observatories](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00899-6%3Fdgcid=raven_jbs_etoc_email/1/01000184814be300-5324a5d9-5c18-4a93-afae-e83f820237fe-000000/7AskP4WdMTb4kUkhio01ItcMhHXloP5LOHx-nT_z8cY=275) Christof Koch, Karel Svoboda, Amy Bernard, Michele A. Basso, Anne K. Churchland, Adrienne L. Fairhall, Peter A. Groblewski, Jérôme A. Lecoq, Zachary F. Mainen, Mackenzie W. Mathis, Shawn R. Olsen, John w. Phillips, Alexandre Pouget, Shreya Saxena, Josh H. Siegle, Anthony M. Zador We propose centralized brain observatories for large-scale recordings of neural activity in mice and non-human primates coupled with cloud-based data analysis and sharing. Such observatories will advance reproducible systems neuroscience and democratize access to the most advanced tools and data. Reviews --------------------------------------------------------------- [Sensing sound: Cellular specializations and molecular force sensors](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00857-1%3Fdgcid=raven_jbs_etoc_email/1/01000184814be300-5324a5d9-5c18-4a93-afae-e83f820237fe-000000/anCQJPiguKP7uJZojJ895s_MIjZUUb_gqzv2Y3bfBoM=275) Xufeng Qiu, Ulrich Müller Qiu and Müller review recent progress in the field of auditory mechanotransduction that has revealed that the mechanotransduction machinery of cochlear hair cells is a complex molecular machine. Notably, hair cell mechanotransduction is not only important for sensory perception but also shapes hair cell morphology and auditory circuits. [Multiscale imaging informs translational mouse modeling of neurological disease](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00811-X%3Fdgcid=raven_jbs_etoc_email/1/01000184814be300-5324a5d9-5c18-4a93-afae-e83f820237fe-000000/KI4JHYQ5hUoo3B1V6IBWpQy4C2Fd4TIWRHY1uXPMdZU=275) Yundi Wang, Jeffrey M. LeDue, Timothy H. Murphy Preclinical multiscale imaging and electrophysiological technology enable exploration of the distributed functional connectivity that underlies symptomology and explain the pathophysiology of neurological disease. These emerging technologies and example use cases are presented in the context of stroke and neurological disorders. Articles --------------------------------------------------------------- [Uncompetitive, adduct-forming SARM1 inhibitors are neuroprotective in preclinical models of nerve injury and disease](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00749-8%3Fdgcid=raven_jbs_etoc_email/1/01000184814be300-5324a5d9-5c18-4a93-afae-e83f820237fe-000000/1u0JSxJG3vXktGWSfkGdp4K5rHaAIB3PZuYG6xit56U=275) Matthew Bratkowski, Thomas C. Burdett, Jean Danao, Xidao Wang, Prakhyat Mathur, Weijing Gu, Jennifer A. Beckstead, Santosh Talreja, Yu-San Yang, Gregory Danko, Jae Hong Park, Mary Walton, Sean P. Brown, Christopher M. Tegley, Prem Raj B. Joseph, Charles H. Reynolds, Shilpa Sambashivan Bratkowski, Burdett, et al. elucidate the molecular basis of NAD-dependent, active-site inhibition of related NAD hydrolases SARM1 and CD38 by compounds that function by forming covalent adducts with a hydrolysis product, ADPR. They show that the SARM1 inhibitors are neuroprotective in preclinical models of nerve injury and disease. [Shear stress activates nociceptors to drive Drosophila mechanical nociception](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00747-4%3Fdgcid=raven_jbs_etoc_email/1/01000184814be300-5324a5d9-5c18-4a93-afae-e83f820237fe-000000/-hLLEWQ14fsS3kPARmovVsg1luNK-LGuC3KxP7op4DI=275) Jiaxin Gong, Jiazhang Chen, Pengyu Gu, Ye Shang, Kendra Takle Ruppell, Ying Yang, Fei Wang, Qi Wen, Yang Xiang How do forces activate mechanical nociceptors? Gong and Chen et al. find that poking a Drosophila larva elicits shear stress to activate nociceptors through select TrpA1 isoforms. Single-channel recordings further demonstrate TrpA1 as a conserved mechanosensitive channel that is specifically activated by shear stress but not stretch. [Activation and expansion of presynaptic signaling foci drives presynaptic homeostatic plasticity](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00748-6%3Fdgcid=raven_jbs_etoc_email/1/01000184814be300-5324a5d9-5c18-4a93-afae-e83f820237fe-000000/7NWOri9GvwMsxdX1IDaq-BB7-3AGrp8W3O0HH3wU5Ns=275) Brian O. Orr, Richard D. Fetter, Graeme W. Davis Open Access Presynaptic homeostatic plasticity (PHP) is an adaptive physiological process that regulates neurotransmission, contributing to nervous system resilience. Orr and colleagues harness both mice and Drosophila to define a presynaptic protein assembly that drives the initiation and expression of PHP, creating a dynamic model for the adaptive control synaptic transmission. [Cell-type-specific integration of feedforward and feedback synaptic inputs in the posterior parietal cortex](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00755-3%3Fdgcid=raven_jbs_etoc_email/1/01000184814be300-5324a5d9-5c18-4a93-afae-e83f820237fe-000000/ayXYLjbbQARsbHFxr1bhLofoNRAyZjWcxY_ErqjK32E=275) Daniel J. Rindner, Archana Proddutur, Gyorgy Lur Open Access Feedforward and feedback pathway interactions are widespread, yet poorly understood. Rindner et al. show that subpopulations of layer 5 pyramidal neurons in the PPC integrate sensory and frontal afferents with distinct nonlinear synaptic dynamics that arise from an interaction of ionic mechanisms and cell-type-specific feedforward inhibition. [Molecularly defined and functionally distinct cholinergic subnetworks](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00796-6%3Fdgcid=raven_jbs_etoc_email/1/01000184814be300-5324a5d9-5c18-4a93-afae-e83f820237fe-000000/MwQNnBAFCi2rnH8JYACZTAas_3dEug_8AUUbI8Ul10E=275) Xinyan Li, Hongyan Yu, Bing Zhang, Lanfang Li, Wenting Chen, Quntao Yu, Xian Huang, Xiao Ke, Yunyun Wang, Wei Jing, Huiyun Du, Hao Li, Tongmei Zhang, Liang Liu, Ling-Qiang Zhu, Youming Lu Li et al. report the discovery of two molecularly defined and functionally distinct D28K+ and D28K− neurons in the medial septum of mice that express mutually exclusive marker genes, show different morphological and physiological properties, and form two distinct subnetworks that play differential roles in the regulation of anxiety-like behavior and spatial memory. [Striatal dopamine explains novelty-induced behavioral dynamics and individual variability in threat prediction](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00758-9%3Fdgcid=raven_jbs_etoc_email/1/01000184814be300-5324a5d9-5c18-4a93-afae-e83f820237fe-000000/ZD94mpSSdHQvGUhipmA9bwSvLszS1y36weYXbChutHE=275) Korleki Akiti, Iku Tsutsui-Kimura, Yudi Xie, Alexander Mathis, Jeffrey E. Markowitz, Rockwell Anyoha, Sandeep Robert Datta, Mackenzie Weygandt Mathis, Naoshige Uchida, Mitsuko Watabe-Uchida Open Access Using automated analysis of mouse behavior, Akiti et al. find diverse and dynamic novelty exploration patterns, including risk assessment, engagement, and neophobia. These behaviors can be explained by a subset of dopamine neurons that treat physical salience as a default threat estimate, thereby causing progressive avoidance of the novel object. [Long-term learning transforms prefrontal cortex representations during working memory](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00858-3%3Fdgcid=raven_jbs_etoc_email/1/01000184814be300-5324a5d9-5c18-4a93-afae-e83f820237fe-000000/YI-wYejGw8JdCPCShh90bSx7ElHE82ylKCqHO7I-nDI=275) Jacob A. Miller, Arielle Tambini, Anastasia Kiyonaga, Mark D’Esposito Miller et al. densely sampled brain activity with human neuroimaging during working memory across months of learning. Long-term training altered the role of the prefrontal cortex, which developed representations for specific stimuli and associations learned over time. Working memory is shaped by long-term experience, which may help resolve competing accounts of prefrontal functioning. [Prefrontal-habenular microstructural impairments in human cocaine and heroin addiction](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00816-9%3Fdgcid=raven_jbs_etoc_email/1/01000184814be300-5324a5d9-5c18-4a93-afae-e83f820237fe-000000/I9xnWl6i-_9N9vcYBvnZQ1Vhl4Yy-4r6Qh4b-EFU9o4=275) Sarah G. King, Pierre-Olivier Gaudreault, Pias Malaker, Joo-won Kim, Nelly Alia-Klein, Junqian Xu, Rita Z. Goldstein The habenula receives direct input from the prefrontal cortex, driving drug-seeking behaviors in preclinical models of addiction. Using diffusion MRI, King et al. identified microstructural abnormalities in the structural connections of the prefrontal cortex and habenula in humans with cocaine or heroin addiction, extending the translational importance of this circuit. [Theory of hierarchically organized neuronal oscillator dynamics that mediate rodent rhythmic whisking](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00756-5%3Fdgcid=raven_jbs_etoc_email/1/01000184814be300-5324a5d9-5c18-4a93-afae-e83f820237fe-000000/1XZVgv-wUUvHH1LEjpQ1BF5n-MlEKy0hlJbxN8NXJMA=275) David Golomb, Jeffrey D. Moore, Arash Fassihi, Jun Takatoh, Vincent Prevosto, Fan Wang, David Kleinfeld Rhythmic whisking is a prominent component of rodent behavior. Golomb et al. solve a hierarchical model of the whisking circuitry. The first whisk within a breathing cycle is derived from inhalation; subsequent whisks arise from an all-inhibitory oscillator. This framework supports longstanding observations of concurrent driven and autonomous motor actions. 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