Original Article

Exp Neurobiol 2018; 27(2): 120-128

Published online April 30, 2018

© The Korean Society for Brain and Neural Sciences

Expression of μ-Opioid Receptor in CA1 Hippocampal Astrocytes

Min-Ho Nam1,2,3†, Kyung-Seok Han1,2,4†, Jaekwang Lee1, Jin Young Bae5, Heeyoung An1,6, Seahyung Park1, Soo-Jin Oh1,2,7, Eunju Kim1, Eunmi Hwang1, Yong Chul Bae5* and C. Justin Lee1,2,4*

1Center for Neuroscience and Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, 2Center for Glia-Neuron Interaction, KIST, Seoul 02792, 3Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, 4Division of Bio-Medical Science &Technology, KIST School, KIST, Seoul 02792, 5Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu 41940, 6KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, 7Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, KIST, Seoul 02792, Korea

Correspondence to: *To whom correspondence should be addressed.
C. Justin Lee, TEL: 82-2-958-6940, FAX: 82-2-958-6937
Yong Chul Bae, TEL: 82-53-660-6860, FAX: 82-53-425-6025
These authors contributed equally.

Received: April 2, 2018; Revised: April 9, 2018; Accepted: April 11, 2018

µ-opioid receptor (MOR) is a class of opioid receptors with a high affinity for enkephalins and beta-endorphin. In hippocampus, activation of MOR is known to enhance the neuronal excitability of pyramidal neurons, which has been mainly attributed to a disinhibition of pyramidal neurons via activating Gαi subunit to suppress the presynaptic release of GABA in hippocampal interneurons. In contrast, the potential role of MOR in hippocampal astrocytes, the most abundant cell type in the brain, has remained unexplored. Here, we determine the cellular and subcellular distribution of MOR in different cell types of the hippocampus by utilizing MOR-mCherry mice and two different antibodies against MOR. Consistent with previous findings, we demonstrate that MOR expression in the CA1 pyramidal layer is co-localized with axon terminals from GABAergic inhibitory neurons but not with soma of pyramidal neurons. More importantly, we demonstrate that MOR is highly expressed in CA1 hippocampal astrocytes. The ultrastructural analysis further demonstrates that the astrocytic MOR is localized in soma and processes, but not in microdomains near synapses. Lastly, we demonstrate that astrocytes in ventral tegmental area and nucleus accumbens also express MOR. Our results provide the unprecedented evidence for the presence of MOR in astrocytes, implicating potential roles of astrocytic MOR in addictive behaviors.

Graphical Abstract

Keywords: Astrocyte, Electron microscopy, Hippocampus, μ-opioid receptor