Neuron: September 4, 2019 (Volume 103, Issue 5)

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Featured Review --------------------------------------------------------------- [Mechanisms of Pathogen Invasion into the Central Nervous System](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30641-5/1/0100016cfcfd8baa-2258f106-1aed-49bd-aa99-8e1477361555-000000/oXlCd46VLpr0xCt6zRH62JZkzzI=125) Cain et al. Online Now --------------------------------------------------------------- [Nucleome Dynamics during Retinal Development](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30686-5/1/0100016cfcfd8baa-2258f106-1aed-49bd-aa99-8e1477361555-000000/-llIrnGY-ySSO7dtIzOtrGpacsg=125) Norrie et al. [Phase Separation-Mediated TARP/MAGUK Complex Condensation and AMPA Receptor Synaptic Transmission](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30685-3/1/0100016cfcfd8baa-2258f106-1aed-49bd-aa99-8e1477361555-000000/6yahWZ4qZTklid6T4RuGJIGCmfU=125) Zeng et al. Video Abstract --------------------------------------------------------------- %2F%2Fyoutu.be%2FoyyvzMwGvGo/1/0100016cfcfd8baa-2258f106-1aed-49bd-aa99-8e1477361555-000000/wzsfp7qbSpCFBDZU-7RitIEIwLc=125 [Drug-like Molecules Decrease Toxic Protein Clumping in ALS](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30524-0/1/0100016cfcfd8baa-2258f106-1aed-49bd-aa99-8e1477361555-000000/ATLmF8FvD63dlxn3AHKa0Rp5zwo=125) Abnormal clumping of proteins such as TDP-43 are thought to cause degeneration of motor neurons in ALS. Fang et al. show that drug-like molecules that alter stress granule formation can reduce abnormal clumping of TDP-43 protein and prolong survival of motor neurons in an ALS disease model. Table of Contents Previews --------------------------------------------------------------- [Bringing Order out of Chaos: Establishing an Epistatic Relationship between CD33 and TREM2](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30703-2%3Fdgcid=raven_jbs_etoc_email/1/0100016cfcfd8baa-2258f106-1aed-49bd-aa99-8e1477361555-000000/rfHC2QlJ-fokyEM2Dc6IfdE2n8o=125) Timothy Y. Huang, Huaxi Xu TREM2 and CD33 are microglial receptors associated with Alzheimer’s disease (AD) risk. In this issue of Neuron, Griciuc et al. (2019) demonstrate opposing effects of CD33 and TREM2 on AD phenotypes, where CD33 deletion promotes neuroprotection in a manner dependent on TREM2. [Memo1 Tiles the Radial Glial Cell Grid](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30705-6%3Fdgcid=raven_jbs_etoc_email/1/0100016cfcfd8baa-2258f106-1aed-49bd-aa99-8e1477361555-000000/lXb7-wKeUPKe2wV6fhEmy7YzDGE=125) Ximena Contreras, Simon Hippenmeyer What are the mechanisms regulating the orderly buildup of the laminated cerebral cortex during development? In this issue of Neuron, Nakagawa et al. (2019) discovered that Memo1 plays a crucial role by mediating the tiling of the radial glial cell grid. [NO Hemodynamic Speed Limit for Hippocampal Neurogenesis](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30704-4%3Fdgcid=raven_jbs_etoc_email/1/0100016cfcfd8baa-2258f106-1aed-49bd-aa99-8e1477361555-000000/3ha4txYzglivqU8AZfVC52lldOI=125) José Manuel Morante-Redolat, Isabel Fariñas In this issue of Neuron, Shen et al. (2019) address the coupling between vascular flow and neurogenic output, showing that pre-existing hippocampal circuits modulate hemodynamics in a NO-dependent manner to promote IGF-1-dependent survival of newly generated neuroblasts. [A Circuit Perspective on State-Dependent Effects of Dopamine Stimulants](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30706-8%3Fdgcid=raven_jbs_etoc_email/1/0100016cfcfd8baa-2258f106-1aed-49bd-aa99-8e1477361555-000000/zQufP74QI0HKiHP2Bg2G08rXt2U=125) Paulius Viskaitis, Denis Burdakov Drugs often target multiple neuronal types. Thus, their behavioral effects may vary according to brain-state-dependent inter-neuronal interactions. In this issue of Neuron, Alhadeff et al. (2019) document hunger and dopamine-dependent alcohol effects, revealing specific circuit-level determinants of variable drug outcomes. [The Value of Persistent Value](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30702-0%3Fdgcid=raven_jbs_etoc_email/1/0100016cfcfd8baa-2258f106-1aed-49bd-aa99-8e1477361555-000000/f4NWOyvZ8h9s7li8eVfWTyLVZqs=125) Frederic M. Stoll, Peter H. Rudebeck In this issue of Neuron, Bari et al. (2019) show that neurons in medial frontal cortex, but not a nearby premotor area, encode the relative value of available options with long-lasting persistent activity states during naturalistic foraging. These long-lasting activity states serve to preferentially guide choices to more likely rewarded options. Neuroview --------------------------------------------------------------- [Device Removal Following Brain Implant Research](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30730-5%3Fdgcid=raven_jbs_etoc_email/1/0100016cfcfd8baa-2258f106-1aed-49bd-aa99-8e1477361555-000000/SEVgKpjt6BWmKU4D-aEJIq6QJjE=125) Demetrio Sierra-Mercado, Peter Zuk, Michael S. Beauchamp, Sameer A. Sheth, Daniel Yoshor, Wayne K. Goodman, Amy L. McGuire, Gabriel Lázaro-Muñoz The development of implanted neural devices to manage neurological and psychiatric disorders or to restore loss of physiological function is a rapidly advancing area of neuroscience research. Sierra-Mercado, Zuk, et al. consider whether investigators of brain implant studies have an obligation to facilitate device explantation for participants who request it at study conclusion. Perspective --------------------------------------------------------------- [Thalamocortical Circuit Motifs: A General Framework](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30555-0%3Fdgcid=raven_jbs_etoc_email/1/0100016cfcfd8baa-2258f106-1aed-49bd-aa99-8e1477361555-000000/wUWmshszJ8KXmEj2o89Qnx-ByyA=125) Michael M. Halassa, S. Murray Sherman Halassa and Sherman highlight the role of the thalamus in cortical function and the lack of knowledge surrounding thalamocortical connectivity at single-cell resolution. They propose thalamocortical motifs as units of organization with potential to inform cognitively relevant functional models. Review --------------------------------------------------------------- [Mechanisms of Pathogen Invasion into the Central Nervous System](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30641-5%3Fdgcid=raven_jbs_etoc_email/1/0100016cfcfd8baa-2258f106-1aed-49bd-aa99-8e1477361555-000000/Bo9jL_uSo8Q0oCCBReF-x9EQ5WY=125) Matthew D. Cain, Hamid Salimi, Michael S. Diamond, Robyn S. Klein Cain et al. provide a comprehensive overview of our current knowledge of the mechanisms by which neurotropic pathogens gain access into the CNS, including those that may be exploited for drug delivery. Neuroresource --------------------------------------------------------------- [A Single-Cell Transcriptomic Atlas of Human Neocortical Development during Mid-gestation](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30561-6%3Fdgcid=raven_jbs_etoc_email/1/0100016cfcfd8baa-2258f106-1aed-49bd-aa99-8e1477361555-000000/sZvhM3jvnIkOCXSZPMomCPSnmfc=125) Damon Polioudakis, Luis de la Torre-Ubieta, Justin Langerman, Andrew G. Elkins, Xu Shi, Jason L. Stein, Celine K. Vuong, Susanne Nichterwitz, Melinda Gevorgian, Carli K. Opland, Daning Lu, William Connell, Elizabeth K. Ruzzo, Jennifer K. Lowe, Tarik Hadzic, Flora I. Hinz, Shan Sabri, William E. Lowry, Mark B. Gerstein, Kathrin Plath, Daniel H. Geschwind An extensive single-cell catalog of cell types in the mid-gestation human neocortex extends our understanding of early cortical development, including subplate neuron transcriptomes, cell-type-specific regulatory networks, brain evolution, and the cellular basis of neuropsychiatric disease. Articles --------------------------------------------------------------- [Small-Molecule Modulation of TDP-43 Recruitment to Stress Granules Prevents Persistent TDP-43 Accumulation in ALS/FTD](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30524-0%3Fdgcid=raven_jbs_etoc_email/1/0100016cfcfd8baa-2258f106-1aed-49bd-aa99-8e1477361555-000000/o-QQ1AiuUgF48emvb_vMrPakyQ0=125) Mark Y. Fang, Sebastian Markmiller, Anthony Q. Vu, Ashkan Javaherian, William E. Dowdle, Philippe Jolivet, Paul J. Bushway, Nicholas A. Castello, Ashmita Baral, Michelle Y. Chan, Jeremy W. Linsley, Drew Linsley, Mark Mercola, Steven Finkbeiner, Eric Lecuyer, Joseph W. Lewcock, Gene W. Yeo Using high-content screening, we identified a class of planar small molecules that can (1) modulate the dynamics of neurodegeneration-linked stress granules (SGs), (2) reduce SG association of ALS-linked RNA-binding proteins, and (3) prevent accumulation of TDP-43 within persistent cytoplasmic puncta. [TREM2 Acts Downstream of CD33 in Modulating Microglial Pathology in Alzheimer’s Disease](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30560-4%3Fdgcid=raven_jbs_etoc_email/1/0100016cfcfd8baa-2258f106-1aed-49bd-aa99-8e1477361555-000000/XsYEm6ZfWQvc9SCX1OkrF03EkJQ=125) Ana Griciuc, Shaun Patel, Anthony N. Federico, Se Hoon Choi, Brendan J. Innes, Mary K. Oram, Gea Cereghetti, Danielle McGinty, Anthony Anselmo, Ruslan I. Sadreyev, Suzanne E. Hickman, Joseph El Khoury, Marco Colonna, Rudolph E. Tanzi Microglial receptors CD33 and TREM2 exhibit opposite effects on Aβ pathology and microglial activity in AD mice. In crosstalk between these receptors, TREM2 is required for differential gene expression in 5xFAD mice deficient for CD33 and acts downstream of CD33. [Memo1-Mediated Tiling of Radial Glial Cells Facilitates Cerebral Cortical Development](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30525-2%3Fdgcid=raven_jbs_etoc_email/1/0100016cfcfd8baa-2258f106-1aed-49bd-aa99-8e1477361555-000000/PDUFRM8Mkri4cFJN1Xtxl_w2JN8=125) Naoki Nakagawa, Charlotte Plestant, Keiko Yabuno-Nakagawa, Jingjun Li, Janice Lee, Chu-Wei Huang, Amelia Lee, Oleh Krupa, Aditi Adhikari, Suriya Thompson, Tamille Rhynes, Victoria Arevalo, Jason L. Stein, Zoltán Molnár, Ali Badache, E.S. Anton Tiled radial glial cells (RGCs) provide an instructive template for the formation of the cerebral cortex. Memo1 regulates RGC tiling underlying radial unit formation and neuronal laminar organization. Mutations in MEMO1 and resultant cortical malformations may contribute to autism risk. [Non-canonical Wnt Signaling through Ryk Regulates the Generation of Somatostatin- and Parvalbumin-Expressing Cortical Interneurons](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30531-8%3Fdgcid=raven_jbs_etoc_email/1/0100016cfcfd8baa-2258f106-1aed-49bd-aa99-8e1477361555-000000/xpxNrxEAzrOYaphLtKfE1KznpBk=125) Melissa G. McKenzie, Lucy V. Cobbs, Patrick D. Dummer, Timothy J. Petros, Michael M. Halford, Steven A. Stacker, Yimin Zou, Gord J. Fishell, Edmund Au Non-canonical Wnt signaling through the Ryk receptor establishes regional subdomains within the MGE along the rostral-caudal axis. These subdomains are defined by graded Ryk signaling, which regulates the proportions of parvalbumin and somatostatin cortical interneurons produced during development. [Control of Synaptic Specificity by Establishing a Relative Preference for Synaptic Partners](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30556-2%3Fdgcid=raven_jbs_etoc_email/1/0100016cfcfd8baa-2258f106-1aed-49bd-aa99-8e1477361555-000000/KFJYM01VKOw5cmEri01J9YDTqGE=125) Chundi Xu, Emma Theisen, Ryan Maloney, Jing Peng, Ivan Santiago, Clarence Yapp, Zachary Werkhoven, Elijah Rumbaut, Bryan Shum, Dorota Tarnogorska, Jolanta Borycz, Liming Tan, Maximilien Courgeon, Ian A. Meinertzhagen, Benjamin de Bivort, Jan Drugowitsch, Matthew Y. Pecot Xu et al. show that in the Drosophila visual system, DIP IgSF proteins are not necessary for synaptogenesis but regulate synaptic specificity by promoting synapses to form between specific cell types. [Neurovascular Coupling in the Dentate Gyrus Regulates Adult Hippocampal Neurogenesis](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30521-5%3Fdgcid=raven_jbs_etoc_email/1/0100016cfcfd8baa-2258f106-1aed-49bd-aa99-8e1477361555-000000/t_hIQvMWNQ3y0JxDmAXO35vvvVo=125) Jia Shen, Depeng Wang, Xinxing Wang, Shashank Gupta, Bhargav Ayloo, Song Wu, Paras Prasad, Qiaojie Xiong, Jun Xia, Shaoyu Ge Metabolic mechanisms may control adult neurogenesis. Shen et al. reveal exploration in an enriched environment elevates blood flow in the dentate gyrus. This exploration-induced hyperemia, under the control of dentate neural circuits, is necessary for experience-induced survival of newborn neurons. [Natural and Drug Rewards Engage Distinct Pathways that Converge on Coordinated Hypothalamic and Reward Circuits](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30526-4%3Fdgcid=raven_jbs_etoc_email/1/0100016cfcfd8baa-2258f106-1aed-49bd-aa99-8e1477361555-000000/3gWwl6BKqZshv5fU5X8vKUa_gPU=125) Amber L. Alhadeff, Nitsan Goldstein, Onyoo Park, Michelle L. Klima, Alexandra Vargas, J. Nicholas Betley How does the brain process natural versus drug rewards? Alhadeff et al. demonstrate that food and drugs signal from the periphery to the hypothalamus via distinct pathways. Furthermore, bidirectional and coordinated interactions between hypothalamic and dopamine circuits potentiate responses to rewards. [Sensory-to-Category Transformation via Dynamic Reorganization of Ensemble Structures in Mouse Auditory Cortex](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30532-X%3Fdgcid=raven_jbs_etoc_email/1/0100016cfcfd8baa-2258f106-1aed-49bd-aa99-8e1477361555-000000/IyKB5krb8m9KXXqbGCI5MHatU7o=125) Yu Xin, Lin Zhong, Yuan Zhang, Taotao Zhou, Jingwei Pan, Ning-long Xu Xin et al. studied the computational mechanism for transforming sensory information into meaningful categories in the auditory cortex using two-photon imaging. Cortical neurons are dynamically recruited to enhance discrimination for stimuli near decision boundaries. Categorical decisions can be accurately decoded from neuronal populations. [Stable Representations of Decision Variables for Flexible Behavior](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30529-X%3Fdgcid=raven_jbs_etoc_email/1/0100016cfcfd8baa-2258f106-1aed-49bd-aa99-8e1477361555-000000/nqpVp3BLz-ZL2Wd9TQTPj54Ej44=125) Bilal A. Bari, Cooper D. Grossman, Emily E. Lubin, Adithya E. Rajagopalan, Jianna I. Cressy, Jeremiah Y. Cohen Flexible behavior requires a memory of previous interactions with the environment. The medial prefrontal cortex persistently represents value-based decision variables, bridging the time between choices. These decision variables are sent to the dorsomedial striatum to bias action selection. [Bayesian Computation through Cortical Latent Dynamics](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30562-8%3Fdgcid=raven_jbs_etoc_email/1/0100016cfcfd8baa-2258f106-1aed-49bd-aa99-8e1477361555-000000/7rHi0aJiS_Cp7RVNX2TJINUGrWQ=125) Hansem Sohn, Devika Narain, Nicolas Meirhaeghe, Mehrdad Jazayeri Sohn et al. found that prior beliefs warp neural representations in the frontal cortex. This warping provides a substrate for the optimal integration of prior beliefs with sensory evidence during sensorimotor behavior. 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