A Novel CCK Receptor GPR173 Mediates Potentiation of GABAergic Inhibition.

Autor:	He L; Departments of Neuroscience.; Biomedical Science.; Research Institute of City University of Hong Kong, Shenzhen 518057, China., Shi H; Departments of Neuroscience.; Biomedical Science.; Research Institute of City University of Hong Kong, Shenzhen 518057, China.; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510070, China., Zhang G; Departments of Neuroscience.; Biomedical Science.; Research Institute of City University of Hong Kong, Shenzhen 518057, China., Peng Y; Departments of Neuroscience.; Biomedical Science.; Research Institute of City University of Hong Kong, Shenzhen 518057, China., Ghosh A; Electrical Engineering, City University of Hong Kong, Kowloon, Hong Kong., Zhang M; Departments of Neuroscience.; Biomedical Science., Hu X; Research Institute of City University of Hong Kong, Shenzhen 518057, China.; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510070, China., Liu C; Innovation Centre for Advanced Interdisciplinary Medicine, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510799, China., Shao Y; Departments of Neuroscience.; Biomedical Science.; Research Institute of City University of Hong Kong, Shenzhen 518057, China., Wang S; Departments of Neuroscience.; Biomedical Science.; Research Institute of City University of Hong Kong, Shenzhen 518057, China., Chen L; Electrical Engineering, City University of Hong Kong, Kowloon, Hong Kong., Sun W; Departments of Neuroscience.; Biomedical Science.; Research Institute of City University of Hong Kong, Shenzhen 518057, China., Su J; Departments of Neuroscience.; Biomedical Science.; Research Institute of City University of Hong Kong, Shenzhen 518057, China., Chen X; Departments of Neuroscience.; Biomedical Science.; Research Institute of City University of Hong Kong, Shenzhen 518057, China., Zhang L; Biomedical Science.; Research Institute of City University of Hong Kong, Shenzhen 518057, China., Chan YS; School of Biomedical Science, University of Hong Kong, Hong Kong., Pei D; Innovation Centre for Advanced Interdisciplinary Medicine, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510799, China.; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510070, China.; Center of Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Hong Kong Academy of Sciences, Hong Kong., Tortorella M; Center of Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Hong Kong Academy of Sciences, Hong Kong., Guo Y; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510070, China., Yan H; Electrical Engineering, City University of Hong Kong, Kowloon, Hong Kong jufanghe@cityu.edu.hk h.yan@cityu.edu.hk., He J; Departments of Neuroscience jufanghe@cityu.edu.hk h.yan@cityu.edu.hk.; Biomedical Science.; Research Institute of City University of Hong Kong, Shenzhen 518057, China.
Jazyk:	angličtina
Zdroj:	The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2023 Mar 29; Vol. 43 (13), pp. 2305-2325. Date of Electronic Publication: 2023 Feb 22.
DOI:	10.1523/JNEUROSCI.2035-22.2023
Abstrakt:	Cholecystokinin (CCK) enables excitatory circuit long-term potentiation (LTP). Here, we investigated its involvement in the enhancement of inhibitory synapses. Activation of GABA neurons suppressed neuronal responses in the neocortex to a forthcoming auditory stimulus in mice of both sexes. High-frequency laser stimulation (HFLS) of GABAergic neurons potentiated this suppression. HFLS of CCK interneurons could induce the LTP of their inhibition toward pyramidal neurons. This potentiation was abolished in CCK knock-out mice but intact in mice with both CCK1R and 2R knockout of both sexes. Next, we combined bioinformatics analysis, multiple unbiased cell-based assays, and histology examinations to identify a novel CCK receptor, GPR173. We propose GPR173 as CCK3R, which mediates the relationship between cortical CCK interneuron signaling and inhibitory LTP in the mice of either sex. Thus, GPR173 might represent a promising therapeutic target for brain disorders related to excitation and inhibition imbalance in the cortex. SIGNIFICANCE STATEMENT CCK, the most abundant and widely distributed neuropeptide in the CNS, colocalizes with many neurotransmitters and modulators. GABA is one of the important inhibitory neurotransmitters, and much evidence shows that CCK may be involved in modulating GABA signaling in many brain areas. However, the role of CCK-GABA neurons in the cortical microcircuits is still unclear. We identified a novel CCK receptor, GPR173, localized in the CCK-GABA synapses and mediated the enhancement of the GABA inhibition effect, which might represent a promising therapeutic target for brain disorders related to excitation and inhibition imbalance in the cortex. (Copyright © 2023 He et al.)
Databáze:	MEDLINE
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