Activation of Astrocytic μ-Opioid Receptor Causes Conditioned Place Preference

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

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

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. Nam et al. demonstrate that activation of hippocampal astrocytic μ-opioid receptor causes glutamate release, which increases the release probability by neuronal presynaptic mGluR1 activation and potentiates synaptic plasticity at the SC-CA1 pathway. This enhanced synaptic transmission and synaptic plasticity account for the acquisition of memory associated with CPP.

Original languageEnglish
Pages (from-to)1154-1166.e5
JournalCell Reports
Volume28
Issue number5
DOIs
Publication statusPublished - 2019 Jul 30

Bibliographical note

Funding Information:
This study was supported by the Creative Research Initiative Program funded by National Research Foundation (NRF) of Korea ( 2015R1A3A2066619 ) and Korea Institute of Science and Technology Institutional Program (project no. 2E26860 ) to C.J.L. and by the NRF of Korea ( 2017R1A5A2015391 ) to Y.C.B.

Funding Information:
This study was supported by the Creative Research Initiative Program funded by National Research Foundation (NRF) of Korea (2015R1A3A2066619) and Korea Institute of Science and Technology Institutional Program (project no. 2E26860) to C.J.L. and by the NRF of Korea (2017R1A5A2015391) to Y.C.B. Conceptualization, M.-H.N. K.-S.H. and C.J.L; Investigation, M.-H.N. K.-S.H. J.L. W.W. W.K. J.Y.B. J.W. J.K. E.K. T.-Y.C. H.C. and S.-B.K.; Resources, K.D.P. S.-Y.C. Y.C.B. and C.J.L.; Writing - original draft preparation, M.-H.N. and K.-S.H.; Writing - review and editing, M.-H.N. K.-S.H. and C.J.L. The authors declare no completing interest.

Publisher Copyright:
© 2019 The Authors

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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