Cortical astrocytes modulate dominance behavior in male mice by regulating synaptic excitatory and inhibitory balance

Kyungchul Noh, Woo Hyun Cho, Byung Hun Lee, Dong Wook Kim, Yoo Sung Kim, Keebum Park, Minkyu Hwang, Ellane Barcelon, Yoon Kyung Cho, C. Justin Lee, Bo Eun Yoon, Se Young Choi, Hye Yoon Park, Sang Beom Jun, Sung Joong Lee

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Social hierarchy is established as an outcome of individual social behaviors, such as dominance behavior during long-term interactions with others. Astrocytes are implicated in optimizing the balance between excitatory and inhibitory (E/I) neuronal activity, which may influence social behavior. However, the contribution of astrocytes in the prefrontal cortex to dominance behavior is unclear. Here we show that dorsomedial prefrontal cortical (dmPFC) astrocytes modulate E/I balance and dominance behavior in adult male mice using in vivo fiber photometry and two-photon microscopy. Optogenetic and chemogenetic activation or inhibition of dmPFC astrocytes show that astrocytes bidirectionally control male mouse dominance behavior, affecting social rank. Dominant and subordinate male mice present distinct prefrontal synaptic E/I balance, regulated by astrocyte activity. Mechanistically, we show that dmPFC astrocytes control cortical E/I balance by simultaneously enhancing presynaptic-excitatory and reducing postsynaptic-inhibitory transmission via astrocyte-derived glutamate and ATP release, respectively. Our findings show how dmPFC astrocyte–neuron communication can be involved in the establishment of social hierarchy in adult male mice.

Original languageEnglish
Pages (from-to)1541-1554
Number of pages14
JournalNature Neuroscience
Volume26
Issue number9
DOIs
StatePublished - Sep 2023

Bibliographical note

Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.

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