Social deprivation induces astrocytic TRPA1-GABA suppression of hippocampal circuits

• Published in: Neuron (Cambridge, Mass.) Mass.), 2023-04, Vol.111 (8), p.1301-1315.e5
• Main Authors: Cheng, Yi-Ting, Woo, Junsung, Luna-Figueroa, Estefania, Maleki, Ehson, Harmanci, Akdes Serin, Deneen, Benjamin
• Format: Article
• Language: English
• Subjects: Animals; astrocyte; Astrocytes - metabolism; GABA; gamma-Aminobutyric Acid - metabolism; hippocampus; Hippocampus - metabolism; Mice; Neurons - metabolism; Social Deprivation; TRPA1; TRPA1 Cation Channel - genetics; TRPA1 Cation Channel - metabolism
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2023.01.015

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. [Display omitted] •Social deprivation alters molecular and cellular properties of hippocampal astrocytes•Astrocytic TRPA1 suppresses mouse hippocampal circuit function after social deprivation•TRPA1 mediates elevated tonic GABA release from astrocytes after social deprivation•Astrocytic GABA suppresses hippocampal circuit function after social deprivation Social experience has a profound impact on cognitive function; yet, experience-dependent roles for astrocytes in brain circuits remain obscure. Using juvenile social deprivation models, Cheng et al. found that astrocyte function is tuned to social experience, identifying context-specific mechanisms by which astrocytic TRPA1 and GABA coordinately suppress hippocampal circuits.