Hippocampal astrocytes modulate anxiety-like behavior

Woo-Hyun Cho (), Kyungchul Noh, Byung Hun Lee, Ellane Barcelon, Sang Beom Jun, Hye Yoon Park and Sung Joong Lee ()
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Woo-Hyun Cho: Seoul National University School of Dentistry
Kyungchul Noh: Seoul National University School of Dentistry
Byung Hun Lee: Seoul National University
Ellane Barcelon: Seoul National University School of Dentistry
Sang Beom Jun: Ewha Womans University
Hye Yoon Park: Seoul National University
Sung Joong Lee: Seoul National University School of Dentistry

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract Astrocytes can affect animal behavior by regulating tripartite synaptic transmission, yet their influence on affective behavior remains largely unclear. Here we showed that hippocampal astrocyte calcium activity reflects mouse affective state during virtual elevated plus maze test using two-photon calcium imaging in vivo. Furthermore, optogenetic hippocampal astrocyte activation elevating intracellular calcium induced anxiolytic behaviors in astrocyte-specific channelrhodopsin 2 (ChR2) transgenic mice (hGFAP-ChR2 mice). As underlying mechanisms, we found ATP released from the activated hippocampal astrocytes increased excitatory synaptic transmission in dentate gyrus (DG) granule cells, which exerted anxiolytic effects. Our data uncover a role of hippocampal astrocytes in modulating mice anxiety-like behaviors by regulating ATP-mediated synaptic homeostasis in hippocampal DG granule cells. Thus, manipulating hippocampal astrocytes activity can be a therapeutic strategy to treat anxiety.

Date: 2022
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DOI: 10.1038/s41467-022-34201-z

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