Activation of Astrocytic μ-Opioid Receptor Causes Conditioned Place Preference
- Activation of Astrocytic μ-Opioid Receptor Causes Conditioned Place Preference
- 박기덕; 남민호; 이승은; 이재광; 우준성; 전희정; 원우진; 한경석; 고우현; 배진영; 김재영; Elliot Kwong; 최태용; 김상범; 최세영; 배용철; 이창준
- Astrocyte; Mu-opioid receptor; Hippocampus; Conditioned place preference; LTP
- Issue Date
- Cell Reports
- VOL 28-1166
- 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.
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