Social Deprivation Induces Astrocytic TRPA1-Gaba Suppression of Hippocampal Circuits

Authors

Yi-Ting Cheng
Junsung Woo
Estefania Luna-Figueroa
Ehson Maleki
Akdes Serin Harmanci
Benjamin Deneen

Publication Date

4-19-2023

Journal

Neuron

DOI

10.1016/j.neuron.2023.01.015

PMID

36787749

PMCID

PMC10121837

PubMedCentral® Posted Date

4-19-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Mice, Animals, Astrocytes, Hippocampus, Neurons, Social Deprivation, gamma-Aminobutyric Acid, TRPA1 Cation Channel

Abstract

Social experience is essential for the development and maintenance of higher order brain function. Social deprivation results in a host of cognitive deficits and cellular studies have largely focused on associated neuronal dysregulation; how astrocyte function is impacted by social deprivation is unknown. Here we show that hippocampal astrocytes from juvenile mice subjected to social isolation exhibit increased Ca2+ activity and global changes in gene expression. We found that the Ca2+ channel TRPA1 is upregulated in astrocytes after social deprivation and astrocyte-specific deletion of TRPA1 reverses the physiological and cognitive deficits associated with social deprivation. Mechanistically, TRPA1 inhibition of hippocampal circuits is mediated by a parallel increase of astrocytic production and release of the inhibitory neurotransmitter GABA after social deprivation. Collectively, our studies reveal how astrocyte function is tuned to social experience and identifies a social context specific mechanism by which astrocytic TRPA1 and GABA coordinately suppress hippocampal circuit function.