Activation of Astrocytic μ-Opioid Receptor Causes Conditioned Place Preference

• DOI: 10.1016/j.celrep.2019.06.071
• Publication Date: 2019-07-30T17:48:16Z
• Authors: Min-Ho Nam; Kyung-Seok Han; Jaekwang Lee; Woojin Won; Wuhyun Koh; Jin Young Bae; Junsung Woo; Jayoung Kim; Elliot Kwong; Tae-Yong Choi; Heejung Chun; Seung Eun Lee; Sang-Bum Kim; Ki Duk Park; Se-Young Choi; Yong Chul Bae; C. Justin Lee
• Keywords: Mice, Knockout; 0301 basic medicine; 0303 health sciences; QH301-705.5; Receptors, Opioid, mu; GTP-Binding Protein alpha Subunits, Gi-Go; Receptors, Metabotropic Glutamate; Mice; 03 medical and health sciences; Memory; Astrocytes; Animals; Biology (General); CA1 Region, Hippocampal

The underlying mechanisms of how positive emotional valence (e.g., pleasure) causes preference of an associated context is poorly understood. Here, we show that activation of astrocytic μ-opioid receptor (MOR) drives conditioned place preference (CPP) by means of specific modulation of astrocytic MOR, an exemplar endogenous Gi protein-coupled receptor (Gi-GPCR), in the CA1 hippocampus. Long-term potentiation (LTP) induced by a subthreshold stimulation with the activation of astrocytic MOR at the Schaffer collateral pathway accounts for the memory acquisition to induce CPP. This astrocytic MOR-mediated LTP induction is dependent on astrocytic glutamate released upon activation of the astrocytic MOR and the consequent activation of the presynaptic mGluR1. The astrocytic MOR-dependent LTP and CPP were recapitulated by a chemogenetic activation of astrocyte-specifically expressed Gi-DREADD hM4Di. Our study reveals that the transduction of inhibitory Gi-signaling into augmented excitatory synaptic transmission through astrocytic glutamate is critical for the acquisition of contextual memory for CPP.