Neuron: November 2, 2022 (Volume 110, Issue 21)

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Featured articles --------------------------------------------------------------- [Microglia states and nomenclature: A field at its crossroads](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00953-9/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/VUT3MgLJVQA3fo3ayePFYCM7KbasOyHPnEEcWPiNlVk=273 ) Paolicelli et al. [The neurobiology of long COVID](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00910-2/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/Exn9JLRn_PuznU_eqqGe9NWFmJz4rE3DrEXuy9VAryU=273 ) Monje and Iwasaki [Microglial efferocytosis: Diving into the Alzheimer’s disease gene pool](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00919-9/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/LknQGdmKNxraeEbxlbOvITSzIc561QPpOze2sy2tUOk=273 ) Romero-Molina et al. [Neuronal regulation of B-cell immunity: Anticipatory immune posturing?](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00918-7/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/XcF9TMB33mzK2ZWyQC2om-PMxqxofMHE9HZltzHQuDY=273 ) You et al. Online now --------------------------------------------------------------- [Mechanosensitive brain tumor cells construct blood-tumor barrier to mask chemosensitivity](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00911-4/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/0-6ZENEJfXqiF43VnDObVJEmYx5yme5Vs1CQrEYFOzA=273) Chen et al. [Inhibitory Kcnip2 neurons of the spinal dorsal horn control behavioral sensitivity to environmental cold](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00912-6/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/AlrZwCuXZfUJ6a3WeZeaVJSo3Z7SvaiogxDA11tQT_I=273) Albisetti et al. [A unified theory for the computational and mechanistic origins of grid cells](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00907-2/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/f430RLJEaZkjfVb9VSQf-7-RyZira_UfeIpd7R37lk4=273) Sorscher et al. [Learning shapes cortical dynamics to enhance integration of relevant sensory input](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00905-9/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/EOL5P77BE_lbQ9XjTbelOozetQjqn7coieZ9SKPAT_Q=273) Chadwick et al. Table of Contents Editorial --------------------------------------------------------------- [Neuro-immune interactions: The spectacular forest](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00956-4%3Fdgcid=raven_jbs_etoc_email/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/lYygXkxarOiUpF85pzelU6XRssMZM-m775eFvJ33FYU=273) Ted Dobie In this special issue of Neuron, we present a series of opinions and reviews on neuro-immune interactions. Recent insights into how profoundly the nervous and immune systems affect each other, bolstered by trans-disciplinary collaboration, have revolutionized both neuroscience and immunology. Like a forest ecosystem, an organism thrives or withers depending on the balance of its components. Highlighted in this special issue is a small sampling of the ever-growing list of diseases influenced by dysfunctional neuro-immune crosstalk, ranging from multiple sclerosis and brain cancer to long COVID and Alzheimer’s. Q&A --------------------------------------------------------------- [Frauke Zipp](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00917-5%3Fdgcid=raven_jbs_etoc_email/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/Kq0iSLXP7rbua1DPMaABDYBR9X3bAqd_SjI_BkD4svo=273) [Larry Steinman](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00916-3%3Fdgcid=raven_jbs_etoc_email/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/UBG2k2WZwrmwNibm3v9g74N9Aelgl_zHW2dqpAd2b7E=273) [Gloria Choi](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00915-1%3Fdgcid=raven_jbs_etoc_email/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/U_ZvO-HYDw4-ehLinj1vhBFyQn6WLf6UlbxCfLmyJlY=273) [Jonathan Kipnis](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00914-X%3Fdgcid=raven_jbs_etoc_email/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/JXq-0cqdyZggwUC3tRwg8zSNXRP_xdo3lMBZ__7eRec=273) NeuroViews --------------------------------------------------------------- [The brain-immune ecosystem: Implications for immunotherapy in defeating neurodegenerative diseases](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00812-1%3Fdgcid=raven_jbs_etoc_email/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/dagHAtpqSmtsteAp3oZxHPVowEneBJOZcm15iuqYw5Q=273) Michal Schwartz, Miguel A. Abellanas, Afroditi Tsitsou-Kampeli, Stefano Suzzi Recent functional and anatomical discoveries of brain-immune relationships have overturned previous beliefs regarding the brain’s immune privilege. Here, we propose that the brain and immune cells at its borders operate as an “ecosystem” to support the brain’s robustness and resilience. Modulation of this ecosystem can be harnessed in the clinic. [Immunoception: Defining brain-regulated immunity](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00920-5%3Fdgcid=raven_jbs_etoc_email/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/XrYwTVYY9uBBIya_-yW-buzv1nEYKaK-gN17OsqzEs8=273) Tamar Koren, Asya Rolls The emerging understanding of homeostatic neuroimmune interactions requires developing relevant terminology. In this NeuroView, Koren and Rolls define “immunoception” as the brain’s bidirectional monitoring and control of immunity. They propose that the physiological trace storing immune-related information, the “immunengram,” is distributed between the brain and memory cells residing in peripheral tissues. Primers --------------------------------------------------------------- [The industrial genomic revolution: A new era in neuroimmunology](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00869-8%3Fdgcid=raven_jbs_etoc_email/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/3Ukqk8rHBAiny_0YR4hnKge21MWri0ecGAY3cq3W-Lo=273) Rotem Shalita, Ido Amit Shalita and Amit outline current and emerging advancements in single-cell multiomics technologies and their applications to neuroimmunology and provide a road map toward deep characterization of fundamental mechanisms of neuro-immune biology by spatial and molecular dissection at the single-cell level. [Advanced in vitro models: Microglia in action](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00908-4%3Fdgcid=raven_jbs_etoc_email/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/K_7dZa-KqhIMShgP9jRLRwFhmoztih-UduJs1F3hKjg=273) Bilal Cakir, Ferdi Ridvan Kiral, In-Hyun Park In this Neuron primer, Cakir, Kiral, and Park outline recent in vitro microglial generation and characterization achievements, applications of in vitro approaches to questions of microglial functions in health and disease, and prospective future enhancements focusing on brain organoid models. Perspectives --------------------------------------------------------------- [Microglia states and nomenclature: A field at its crossroads](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00953-9%3Fdgcid=raven_jbs_etoc_email/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/IQoE66DF2hdfLWwlqvFoA7p_LhNSfTh8YIgJV9gWm8Y=273) Rosa C. Paolicelli, Amanda Sierra, Beth Stevens, Marie-Eve Tremblay, Adriano Aguzzi, Bahareh Ajami, Ido Amit, Etienne Audinat, Ingo Bechmann, Mariko Bennett, Frederick Bennett, Alain Bessis, Knut Biber, Staci Bilbo, Mathew Blurton-Jones, Erik Boddeke, Dora Brites, Bert Brône, Guy C. Brown, Oleg Butovsky, Monica J. Carson, Bernardo Castellano, Marco Colonna, Sally A. Cowley, Colm Cunningham, Dimitrios Davalos, Philip L. De Jager, Bart de Strooper, Adam Denes, Bart J.L. Eggen, Ukpong Eyo, Elena Galea, Sonia Garel, Florent Ginhoux, Christopher K. Glass, Ozgun Gokce, Diego Gomez-Nicola, Berta González, Siamon Gordon, Manuel B. Graeber, Andrew D. Greenhalgh, Pierre Gressens, Melanie Greter, David H. Gutmann, Christian Haass, Michael T. Heneka, Frank L. Heppner, Soyon Hong, David A. Hume, Steffen Jung, Helmut Kettenmann, Jonathan Kipnis, Ryuta Koyama, Greg Lemke, Marina Lynch, Ania Majewska, Marzia Malcangio, Tarja Malm, Renzo Mancuso, Takahiro Masuda, Michela Matteoli, Barry W. McColl, Veronique E. Miron, Anna Victoria Molofsky, Michelle Monje, Eva Mracsko, Agnes Nadjar, Jonas J. Neher, Urte Neniskyte, Harald Neumann, Mami Noda, Bo Peng, Francesca Peri, V. Hugh Perry, Phillip G. Popovich, Clare Pridans, Josef Priller, Marco Prinz, Davide Ragozzino, Richard M. Ransohoff, Michael W. Salter, Anne Schaefer, Dorothy P. Schafer, Michal Schwartz, Mikael Simons, Cody J. Smith, Wolfgang J. Streit, Tuan Leng Tay, Li-Huei Tsai, Alexei Verkhratsky, Rommy von Bernhardi, Hiroaki Wake, Valérie Wittamer, Susanne A. Wolf, Long-Jun Wu, Tony Wyss-Coray A group of multidisciplinary experts discusses the current understanding of microglial states as a dynamic concept and the importance of addressing microglial function. Conceptual framework and recommendations on microglial nomenclature are provided, serving as foundations for a future white paper. [The neurobiology of long COVID](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00910-2%3Fdgcid=raven_jbs_etoc_email/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/MzeMQJxsCmnOSS5IAAzHIAUUIEN3goRTlie6XzAL27I=273) Michelle Monje, Akiko Iwasaki Open Access Persistent neurological symptoms affect a substantial fraction of people after COVID-19 and represent a major component of long COVID. Here, Monje and Iwasaki review what is understood about the neurobiological underpinnings of long COVID cognitive symptoms. [The CNS mononuclear phagocyte system in health and disease](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00909-6%3Fdgcid=raven_jbs_etoc_email/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/mCArZk58XYqbMHAHm7CDXOXSLrtRz91u2LjkKIdTuII=273) Sarah Mundt, Melanie Greter, Burkhard Becher The CNS harbors distinct subsets of mononuclear phagocytes, including parenchymal microglia and CNS border-associated macrophages and patrolling monocytes and dendritic cells. In this issue of Neuron, Mundt et al. discuss recent findings on their specific functions in health and disease. Reviews --------------------------------------------------------------- [Microglial efferocytosis: Diving into the Alzheimer’s disease gene pool](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00919-9%3Fdgcid=raven_jbs_etoc_email/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/Tv_aufQqQJKVqKBqWErXMssI0_4eNcVkawXhRpOZxcQ=273) Carmen Romero-Molina, Francesca Garretti, Shea J. Andrews, Edoardo Marcora, Alison M. Goate Romero-Molina, Garretti, and colleagues illustrate their hypothesis that genetic variants associated with AD modulate disease susceptibility by affecting genes and pathways that play critical roles in efferocytosis, the phagocytic clearance of cholesterol-rich cellular debris by macrophages like microglia. [Microglia in multiple sclerosis: Protectors turn destroyers](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00602-X%3Fdgcid=raven_jbs_etoc_email/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/gtDOtT_ou4I_runv2E2br-DS5SngS3_LEenl_dzLwyk=273) V. Wee Yong The benefits of microglia appear to be derailed in multiple sclerosis where they assume injurious roles. Yong reviews the protector-gone-rogue activities of microglia, considers the mechanisms underlying this switch, and discusses medications to normalize microglia in multiple sclerosis. [CNS remyelination and inflammation: From basic mechanisms to therapeutic opportunities](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00862-5%3Fdgcid=raven_jbs_etoc_email/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/g1HTNtxlJrsTt-Pr7iQAQGuPbxFK51kPdozMln0DySw=273) Robin J.M. Franklin, Mikael Simons In this review, Franklin and Simons discuss the role of inflammation, in particular innate immunity, in remyelination, describing its many and complex facets and discussing how our evolving understanding can be harnessed to translational goals. [Perivascular spaces and their role in neuroinflammation](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00957-6%3Fdgcid=raven_jbs_etoc_email/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/Zt-iKvhaePYZmvfK_DdvI5TC5wmWXo3N999vC_R5bO0=273) Benjamin V. Ineichen, Serhat V. Okar, Steven T. Proulx, Britta Engelhardt, Hans Lassmann, Daniel S. Reich In this review, Ineichen and colleagues summarize the role of the perivascular space in neuroinflammation and describe how those spaces can be visualized, as well as the cell types involved. Based on this, they propose a model of the cascade of events during neuroinflammation. [Neuronal regulation of B-cell immunity: Anticipatory immune posturing?](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00918-7%3Fdgcid=raven_jbs_etoc_email/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/Q01yrb3xIE8h9YR5N1nVUCjPM5rjJjoWaIV_6JCZpXc=273) Zhiwei You, Bo Liu, Hai Qi It is increasingly appreciated that the brain regulates operation of the immune system. In this review, Qi and colleagues discuss in depth how the B cell immune response and antibody-mediated immunity are controlled by the brain. [The sympathetic nervous system in the 21st century: Neuroimmune interactions in metabolic homeostasis and obesity](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00946-1%3Fdgcid=raven_jbs_etoc_email/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/F_suflIpr9IoOx_xlljNb48xL4wFIuZ0IwRCENgjX38=273) Noelia Martinez-Sanchez, Owen Sweeney, Davi Sidarta-Oliveira, Alexandre Caron, Sarah A. Stanley, Ana I. Domingos In this review, we update the neuroanatomical maps of sympathetic innervation of the pancreas, liver, and adipose tissues. We discuss the role of the immune cells in regulating sympathetic terminals and metabolism. We conjecture on novel anti-obesity therapies that could emerge from the modern appreciation of SNS as a neural network modulated by immune cells. [Bioelectronic medicine: Preclinical insights and clinical advances](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00808-X%3Fdgcid=raven_jbs_etoc_email/1/010001843927f6d7-a7d12bf9-dfbe-4bdb-8c4d-64d066023415-000000/m-rKrnT7Q7kMHhv1zIg7KrQyiWj2wf69sXt7JWhOL3A=273) Valentin A. Pavlov, Kevin J. Tracey In this review, Pavlov and Tracey discuss recent findings and developments in the growing field of bioelectronic medicine with current clinical implications in the treatment of inflammatory diseases and many other disorders and conditions. 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