Woo-Hyun Cho1,7 , Kyungchul Noh1,7, Byung Hun Lee2, Ellane Barcelon1, Sang Beom Jun 3,4,5, Hye Yoon Park2,6 & Sung Joong Lee1
1Department of Physiology and Neuroscience, Dental Research Institute, Seoul National University School of Dentistry, Seoul 08826, Republic of Korea.
2Department of Physics and Astronomy, Seoul National University, Seoul 08826, Republic of Korea.
3Department of Electronic and Electrical Engineering, Ewha Womans University, Seoul 03760, Republic of Korea.
4Graduate Program in Smart Factory, Ewha Womans University, Seoul 03760, Republic of Korea.
5Department of Brain & Cognitive Sciences, Ewha Womans University, Seoul 03760, Republic of Korea.
6Department of Electrical and Computer Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
7These authors contributed equally: Woo-Hyun Cho, Kyungchul Noh.
Corresponding authors : Correspondence to Woo-Hyun Cho or Sung Joong Lee.
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.