Astrocytes are a large and diverse population of morphologically complex cells that exist throughout nervous systems of multiple species. Progress over the last two decades has shown that astrocytes mediate developmental, physiological, and pathological processes. However, a long-standing open question is how astrocytes regulate neural circuits in ways that are behaviorally consequential. In this regard, we summarize recent studies using Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, and Mus musculus. The data reveal diverse astrocyte mechanisms operating in seconds or much longer timescales within neural circuits and shaping multiple behavioral outputs. We also refer to human diseases that have a known primary astrocytic basis. We suggest that including astrocytes in mechanistic, theoretical, and computational studies of neural circuits provides new perspectives to understand behavior, its regulation, and its disease-related manifestations. In this review, Nagai et al. summarize recent findings and provide an interpretative framework for diverse astrocyte mechanisms regulating neural circuit functions and animal behavior in multiple species, including C. elegans, Drosophila melanogaster, Danio rerio, and Mus musculus.
Bibliographical noteFunding Information:
J.N. and X.Y. were supported by Khakh lab funds during this work. T.P. was supported by a NARSAD Young Investigator Grant (Brain & Behavior Research Foundation, 28616), a McDonnell Center for Cellular and Molecular Neurobiology grant (22-3930-26275U), and a Whitehall Foundation Inc. research grant (2020-08-35). E.C. was supported by the National Research Foundation of Korea (NRF) (2017R1A2B3011098, 2017M3C7A1023471, and 2020R1A4A1019009). M.R.F. was supported by R01 NS053538. K.R.M. is supported by the NIH (1R21NS115437). M.H.H. was supported by the Medical Research Council, UK. (MC_U105170643). P.G.H. is supported by grants from the NIH (5RO1 NS037585-22, 5RO1 NS107315-03, and 1RO1 AG061838-01). D.R. is a Wellcome Trust Senior Investigator. S.S. was supported by NIH grant R35NS105094. B.S.K. was supported by the NIH (R35NS111583 and DA047444), CHDI Inc., an Allen Distinguished Investigator Award, a Paul G. Allen Frontiers Group advised grant of the Paul G. Allen Family Foundation, and the Ressler Family Foundation. J.N. and X.Y. wrote first drafts of the species sections; all other authors expanded and revised them along lines of expertise. B.S.K. wrote the summary, opening, and closing sections and assembled comments from all authors. B.S.K. wrote the final version; all others commented.
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