Neuron: May 19, 2021 (Volume 109, Issue 10)

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[View the collection](%2F%2Fwww.cell.com%2Fcell-systems%2Fcollections%2Fbiotechnology%3Futm_campaign=STMJ_1619210834_SC%26utm_medium=email%26utm_source=Other%26dgcid=STMJ_1619210834_SC/2/010001798575eec1-73ebb0cd-e0e6-4709-bd06-bac94f334514-000000/vK4Uc3XJvfYIbXzlKVEI0vPw4PrRmpJb9gWRyJoAqoI=193) Featured review --------------------------------------------------------------- [Neural circuits of social behaviors: Innate yet flexible](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00112-4/1/010001798575eec1-73ebb0cd-e0e6-4709-bd06-bac94f334514-000000/NXAmEI7NbaaURm7gF8prrN16oQfM1_EnngUMFU3Bod4=193) Wei et al. Featured Q&A --------------------------------------------------------------- [Mark Mattson Q&A Interview](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00116-1/1/010001798575eec1-73ebb0cd-e0e6-4709-bd06-bac94f334514-000000/ga6yO-eXW6XhzbislS5tPVwv4dauJE_xsOw6OBdI5OM=193) Neuroresource --------------------------------------------------------------- [Efficient optogenetic silencing of neurotransmitter release with a mosquito rhodopsin](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00161-6/1/010001798575eec1-73ebb0cd-e0e6-4709-bd06-bac94f334514-000000/8qv0nYU4Env8sxAFZ4a4qJdTa8hd1KK_sTC7bZupDgQ=193) Mahn et al. Online now --------------------------------------------------------------- [Periphery signals generated by Piezo-mediated stomach stretch and Neuromedin-mediated glucose load regulate the Drosophila brain nutrient sensor](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00324-X/1/010001798575eec1-73ebb0cd-e0e6-4709-bd06-bac94f334514-000000/zs2nw3EZ_UPpZzK9lPdrVWKZyTCMlaHEvVZxAijAyU4=193) Oh et al. [No consolidation without representation: Correspondence between neural and psychological representations in recent and remote memory](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00291-9/1/010001798575eec1-73ebb0cd-e0e6-4709-bd06-bac94f334514-000000/hkmY69jzGaniyrVmLjxpMgf5ok2-6SYNfqs0u4rK78w=193) Gilboa et al. [How does hemispheric specialization contribute to human-defining cognition?](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00290-7/1/010001798575eec1-73ebb0cd-e0e6-4709-bd06-bac94f334514-000000/fQdeVE2MQSpUL-mz2514MBHv57ku57-CjUfBv_2trdQ=193) Hartwigsen et al. [UBQLN2-HSP70 axis reduces poly-Gly-Ala aggregates and alleviates behavioral defects in the C9ORF72 animal model](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00289-0/1/010001798575eec1-73ebb0cd-e0e6-4709-bd06-bac94f334514-000000/T7fwIh5G5AxQNNwcsmK0trz-rx09L_xXB7ILm8O4now=193) Zhang et al. Table of Contents Previews --------------------------------------------------------------- [Ophn1 regulation of prefrontal inhibition: A mechanism for stress susceptibility in intellectual disability](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00326-3%3Fdgcid=raven_jbs_etoc_email/1/010001798575eec1-73ebb0cd-e0e6-4709-bd06-bac94f334514-000000/n-DUikEZ6t3upI-TbZHkkC0zbRQT-wvMirIUIeEThQI=193) Vedrana Cvetkovska, Rosemary C. Bagot Wang et al. (2021) characterize the molecular, cellular, and circuit-level role of Oligophrenin-1 in prefrontal parvalbumin interneurons, demonstrating that loss of Ophn1 function in these neurons is a mechanism for increased susceptibility to stress in intellectual disability caused by OPHN1 mutations. [Tau heckles speckles: A pathogenic mechanism in tauopathy?](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00288-9%3Fdgcid=raven_jbs_etoc_email/1/010001798575eec1-73ebb0cd-e0e6-4709-bd06-bac94f334514-000000/ai7j7rLwZcpQCcIFO_k7VTR60T4msDMWoMQGZtsaP1Y=193) Erica L. Gorenberg, James Shorter Protein aggregates can sequester RNA in neurodegenerative disease, but the exact RNAs sequestered by tau inclusions have remained uncharacterized. In this issue of Neuron, Lester et al. (2021) begin to identify these RNAs and reveal related perturbations in nuclear speckles. [Basal ganglia reign through downstream control of motor centers in midbrain and brain stem while updating cortex with efference copy information](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00281-6%3Fdgcid=raven_jbs_etoc_email/1/010001798575eec1-73ebb0cd-e0e6-4709-bd06-bac94f334514-000000/02EfOas1n2oIbLF7CVcePR6bnUr4MSRfCV700WgB3mQ=193) Sten Grillner, William Scott Thompson In this issue of Neuron, McElvain et al. (2021) show that the major output of the basal ganglia, the substantia nigra pars reticulata, targets no fewer than 42 midbrain and brainstem structures and conveys an efference copy of the downstream commands back via thalamus to the cortex and striatum. [Multimodal patterns of inhibitory activity in cerebellar cortex](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00325-1%3Fdgcid=raven_jbs_etoc_email/1/010001798575eec1-73ebb0cd-e0e6-4709-bd06-bac94f334514-000000/EWK19rGf_ADRdL3dmC_40OmgISc3IxtIJ69GJ7qFLEY=193) Chie Satou, Rainer W. Friedrich In this issue of Neuron, Gurnani and Silver (2021) report that activity across Golgi cells, a major type of inhibitory interneuron in the cerebellar cortex, is multidimensional and modulated by behavior. These results suggest multiple functions for inhibition in cerebellar computations. Spotlight --------------------------------------------------------------- [Fast-Trk(B)ing the mechanism of antidepressants](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00323-8%3Fdgcid=raven_jbs_etoc_email/1/010001798575eec1-73ebb0cd-e0e6-4709-bd06-bac94f334514-000000/IwCFju5p-fz49ItN57BQHXyCFgzDUArODTNRrUy1l38=193) Jacinta N. Conroy, Dhanisha J. Jhaveri, Elizabeth J. Coulson The mechanism by which antidepressants elicit clinical improvements has proven elusive. In a recent publication in Cell, Casarotto et al. (2021) reveal a surprising direct interaction between antidepressants and TrkB. This link provides an important mechanistic insight into synaptic remodeling that may assist in the design of improved antidepressant therapeutics. Q&A --------------------------------------------------------------- [Mark Mattson Q&A Interview](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00116-1%3Fdgcid=raven_jbs_etoc_email/1/010001798575eec1-73ebb0cd-e0e6-4709-bd06-bac94f334514-000000/a5HBSblsZCk0Huvy49JDRh1ECYUpTJkeVUx1F9XdNTc=193) Review --------------------------------------------------------------- [Neural circuits of social behaviors: Innate yet flexible](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00112-4%3Fdgcid=raven_jbs_etoc_email/1/010001798575eec1-73ebb0cd-e0e6-4709-bd06-bac94f334514-000000/b0M0iWczcYmBAX93iNQ0Y_HRcHD756s21K5t_MxUvaU=193) Dongyu Wei, Vaishali Talwar, Dayu Lin Social behaviors such as aggression are innate but flexible. In this review, Wei et al. summarize our current understanding of the neural circuits underlying social behaviors in rodents and the plasticity in the circuits that supports behavioral flexibility. NeuroResource --------------------------------------------------------------- [Efficient optogenetic silencing of neurotransmitter release with a mosquito rhodopsin](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00161-6%3Fdgcid=raven_jbs_etoc_email/1/010001798575eec1-73ebb0cd-e0e6-4709-bd06-bac94f334514-000000/UyLBAW_K8Am9fxPuqba6qiasBjYLPHKAR-jDMXnL3XE=193) Mathias Mahn, Inbar Saraf-Sinik, Pritish Patil, Mauro Pulin, Eyal Bitton, Nikolaos Karalis, Felicitas Bruentgens, Shaked Palgi, Asaf Gat, Julien Dine, Jonas Wietek, Ido Davidi, Rivka Levy, Anna Litvin, Fangmin Zhou, Kathrin Sauter, Peter Soba, Dietmar Schmitz, Andreas Lüthi, Benjamin R. Rost, J. Simon Wiegert, Ofer Yizhar This study describes the engineering, validation, and application of a novel optogenetic tool, eOPN3, based on a mosquito homolog of encephalopsin. Illumination of eOPN3-expressing synaptic terminals leads to robust and stable suppression of synaptic transmission through activation of inhibitory G protein signaling. Articles --------------------------------------------------------------- [Oligophrenin-1 moderates behavioral responses to stress by regulating parvalbumin interneuron activity in the medial prefrontal cortex](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00186-0%3Fdgcid=raven_jbs_etoc_email/1/010001798575eec1-73ebb0cd-e0e6-4709-bd06-bac94f334514-000000/JSphBGdMDo7RuojLFjxW5uTOKZg3KlfStCB1J2PdQZ4=193) Minghui Wang, Nicholas B. Gallo, Yilin Tai, Bo Li, Linda Van Aelst Wang et al. show that deficiency of the intellectual disability gene Ophn1 enhances stress-induced helpless/depressive-like behavior. This phenotype is mediated by a diminished excitatory drive onto Ophn1-deficient parvalbumin interneurons in the prelimbic medial prefrontal cortex, leading to hyperactivity in this region. Suppressing neuronal activity or RhoA/Rho-kinase signaling reverses helpless behavior. [Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00194-X%3Fdgcid=raven_jbs_etoc_email/1/010001798575eec1-73ebb0cd-e0e6-4709-bd06-bac94f334514-000000/6naLbn8h3XnSzVfNO-2eFCe72jOaCZM80L7xUqg8cHw=193) Chao Wang, Monica Xiong, Maud Gratuze, Xin Bao, Yang Shi, Prabhakar Sairam Andhey, Melissa Manis, Caitlin Schroeder, Zhuoran Yin, Charlotte Madore, Oleg Butovsky, Maxim Artyomov, Jason D. Ulrich, David M. Holtzman Wang et al. demonstrate that removal of astrocytic APOE4 decreases tau-mediated brain atrophy and synaptic loss, as well as ameliorating disease-associated gene signatures in multiple cell types. Removal of astrocytic APOE4 even after the onset of neurodegeneration reduces tauopathy and tau-mediated neurodegeneration. [Tau aggregates are RNA-protein assemblies that mislocalize multiple nuclear speckle components](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00196-3%3Fdgcid=raven_jbs_etoc_email/1/010001798575eec1-73ebb0cd-e0e6-4709-bd06-bac94f334514-000000/vDdpN0eMGc6grjvCE398MxkGv_Yb-NkrvFEVBrkQ9Kc=193) Evan Lester, Felicia K. Ooi, Nadine Bakkar, Jacob Ayers, Amanda L. Woerman, Joshua Wheeler, Robert Bowser, George A. Carlson, Stanley B. Prusiner, Roy Parker Insoluble tau aggregates are present in multiple neurodegenerative diseases, including Alzheimer’s disease. In this article, Lester et al. show that tau aggregates are enriched for snRNAs and snoRNAs, alter splicing speckles, and mislocalize nuclear splicing proteins. This could help explain RNA processing defects seen in individuals with tau pathology. [Nonlinear spatial integration in retinal bipolar cells shapes the encoding of artificial and natural stimuli](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00185-9%3Fdgcid=raven_jbs_etoc_email/1/010001798575eec1-73ebb0cd-e0e6-4709-bd06-bac94f334514-000000/VSL3kUET-S0ul_ysr3pZ5Ttdza2yuDsY7FE6q5aFOQI=193) Helene Marianne Schreyer, Tim Gollisch Open Access Nonlinear processing in the vertebrate visual system under daylight conditions is often thought to first arise at the output of retinal bipolar cells. Schreyer and Gollisch report that certain bipolar cells in salamander retina already nonlinearly combine their inputs and thereby retain high sensitivity to spatial details of visual stimuli. [Spatial integration during active tactile sensation drives orientation perception](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00190-2%3Fdgcid=raven_jbs_etoc_email/1/010001798575eec1-73ebb0cd-e0e6-4709-bd06-bac94f334514-000000/ly5FwAEa_DuOAoejnlGvO1n3J35fwv2fn9OHR25anJU=193) Jennifer Brown, Ian Antón Oldenburg, Gregory I. Telian, Sandon Griffin, Mieke Voges, Vedant Jain, Hillel Adesnik Integration of tactile input across active sensors is critical for perception. Brown et al. show that mice summate tactile input from multiple whiskers in an arc to discriminate the orientation of an object. Correspondingly, populations of neurons in the barrel cortex integrate multi-whisker input to encode the orientation of objects, and their activity is critical for task performance. [Specific populations of basal ganglia output neurons target distinct brain stem areas while collateralizing throughout the diencephalon](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00187-2%3Fdgcid=raven_jbs_etoc_email/1/010001798575eec1-73ebb0cd-e0e6-4709-bd06-bac94f334514-000000/6P1QbkDaoLVg4T5VGBDKeItWlMU6aZnApX0q25VweH8=193) Lauren E. McElvain, Yuncong Chen, Jeffrey D. Moore, G. Stefano Brigidi, Brenda L. Bloodgood, Byung Kook Lim, Rui M. Costa, David Kleinfeld McElvain et al. map the complete set of brain-wide projections from the largest output nucleus of the murine basal ganglia, the substantia nigra pars reticulata. Spatially segregated and electrophysiologically distinct subpopulations are revealed that project to different brain stem regions along with extensive collaterals to the pedunculopontine nucleus and diencephalon targets. [Multidimensional population activity in an electrically coupled inhibitory circuit in the cerebellar cortex](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00197-5%3Fdgcid=raven_jbs_etoc_email/1/010001798575eec1-73ebb0cd-e0e6-4709-bd06-bac94f334514-000000/TTggRDFnqyPNOunPIDFazSVq-95SNvudNEozvjNHmpU=193) Harsha Gurnani, R. Angus Silver Open Access Inhibitory interneurons orchestrate the activity of neural circuits, but little is known about their population dynamics. By using 3D random-access calcium imaging, Gurnani and Silver show that cerebellar Golgi cell circuits exhibit multidimensional activity with common and distributed modes. A biologically detailed circuit model implicates electrical coupling in shaping the population dynamics. Snapshot --------------------------------------------------------------- [SnapShot: Neuronal dysfunction in inflammation](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00153-7%3Fdgcid=raven_jbs_etoc_email/1/010001798575eec1-73ebb0cd-e0e6-4709-bd06-bac94f334514-000000/m_9ccDt3k1aAVMIH7A-L5ZVF9Xy8TnBeKf3jdvp4_Nk=193) Matthias Kneussel, Manuel A. Friese Neuronal function relies on tightly controlled cytoskeleton transport with adaptive cargo trafficking as prerequisite for synaptic transmission. During inflammation in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), axonal transport efficiency declines, followed by neurodegeneration. Furthermore, neuroinflammation causes an imbalance between excitatory and inhibitory transmission, triggering synaptic dysfunction and loss. Recent data suggest that neuronal transport and synaptic deficits during neuroinflammation are functionally interconnected. To view this SnapShot, open or download the PDF. 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