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Astrocyte regulation of synaptic signaling in psychiatric disorders

Abstract

Over the last 15 years, the field of neuroscience has evolved toward recognizing the critical role of astroglia in shaping neuronal synaptic activity and along with the pre- and postsynapse is now considered an equal partner in tripartite synaptic transmission and plasticity. The relative youth of this recognition and a corresponding deficit in reagents and technologies for quantifying and manipulating astroglia relative to neurons continues to hamper advances in understanding tripartite synaptic physiology. Nonetheless, substantial advances have been made and are reviewed herein. We review the role of astroglia in synaptic function and regulation of behavior with an eye on how tripartite synapses figure into brain pathologies underlying behavioral impairments in psychiatric disorders, both from the perspective of measures in postmortem human brains and more subtle influences on tripartite synaptic regulation of behavior in animal models of psychiatric symptoms. Our goal is to provide the reader a well-referenced state-of-the-art understanding of current knowledge and predict what we may discover with deeper investigation of tripartite synapses using reagents and technologies not yet available.

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Fig. 1: Astroglial regulation of excitatory synapses.
Fig. 2: Astroglial regulation of inhibitory synapses.
Fig. 3: Neuromodulation by astroglia.

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Funding

This review was sponsored in part by the National Institutes of Health (DA007288 and DA044782, AK; DA046373 and DA012513, PWK; DA054154, MDS) and the Veterans administration (BX004727, PWK).

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All three authors contributed equally in writing this review.

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Correspondence to Peter W. Kalivas or Michael D. Scofield.

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Kruyer, A., Kalivas, P.W. & Scofield, M.D. Astrocyte regulation of synaptic signaling in psychiatric disorders. Neuropsychopharmacol. 48, 21–36 (2023). https://doi.org/10.1038/s41386-022-01338-w

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