Abstract
The participation of astrocytes in brain computation was hypothesized in 1992, coinciding with the discovery that these cells display a form of intracellular Ca2+ signaling sensitive to neuroactive molecules. This finding fostered conceptual leaps crystalized around the idea that astrocytes, once thought to be passive, participate actively in brain signaling and outputs. A multitude of disparate roles of astrocytes has since emerged, but their meaningful integration has been muddied by the lack of consensus and models of how we conceive the functional position of these cells in brain circuitry. In this Perspective, we propose an intuitive, data-driven and transferable conceptual framework we coin ‘contextual guidance’. It describes astrocytes as ‘contextual gates’ that shape neural circuitry in an adaptive, state-dependent fashion. This paradigm provides fresh perspectives on principles of astrocyte signaling and its relevance to brain function, which could spur new experimental avenues, including in computational space.
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Data availability
The datasets generated and/or analyzed during the current study are available from the corresponding author upon request.
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Codes and mathematical algorithms used in Fig. 4 will be made available upon publication.
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Acknowledgements
C.M.-R. was supported by a Canadian Institutes of Health Research Project Grant (478629), an NSERC Discovery Grant (RGPIN-2021-03211), Fonds de Recherche du Québec – Santé (296562 & 309889) and the Brain & Behavior Research Foundation (NARSAD Young Investigator Award 28589). S.C. was supported by the Department of Defense (DoD; W911NF-21-1-0312) and the National Science Foundation (1653589). T.P. was supported by the National Institutes of Health (1R01MH127163-01), the DoD (W911NF-21-1-0312), the Brain & Behavior Research Foundation (NARSAD Young Investigator Award 28616), the Whitehall Foundation (2020-08-35) and the McDonnell Center for Cellular and Molecular Neurobiology Award (22-3930-26275U). The authors thank J. Dunphy for critical feedback. We apologize that the work of many of our colleagues and peers could not be cited owing to strict space limitations and the abundance of papers published during the publication process. Figure 4 was created with BioRender.com.
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T.P. wrote the first drafts and created the figures, box and supplementary tables. C.M.-R. and S.C. contributed to sections along lines of expertise. C.M.-R. expanded and revised the manuscript. S.C. generated Fig. 4. T.P. assembled comments from all authors, wrote the final version and performed revisions.
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Murphy-Royal, C., Ching, S. & Papouin, T. A conceptual framework for astrocyte function. Nat Neurosci 26, 1848–1856 (2023). https://doi.org/10.1038/s41593-023-01448-8
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DOI: https://doi.org/10.1038/s41593-023-01448-8