A Novel CCK Receptor GPR173 Mediates Potentiation of GABAergic Inhibition

• DOI: 10.1523/jneurosci.2035-22.2023
• Publication Date: 2023-02-22T18:55:13Z
• Authors: Ling He; Heng Shi; Ge Zhang; Yujie Peng; Avirup Ghosh; Mengfan Zhang; Xiaofeng Hu; Chunhua Liu; Yue Shao; Shujie Wang; Lijiang Chen; Wenjian Sun; Junfeng Su; Xi Chen; Liang Zhang; Ying-Shing Chan; Duanqing Pei; Micky Tortorella; Yiping Guo; Hong Yan; Jufang He
• Keywords: Neocortex; Interneuron; LTP induction

Cholecystokinin (CCK) enables excitatory circuit long-term potentiation (LTP). Here, we investigated its involvement in the enhancement of inhibitory synapses. Activation GABA neurons suppressed neuronal responses neocortex to a forthcoming auditory stimulus mice both sexes. High-frequency laser stimulation (HFLS) GABAergic potentiated this suppression. HFLS CCK interneurons could induce LTP their inhibition toward pyramidal neurons. This was abolished knock-out but intact with CCK1R and 2R knockout Next, combined bioinformatics analysis, multiple unbiased cell-based assays, histology examinations identify novel receptor, GPR173. We propose GPR173 as CCK3R, which mediates relationship between cortical interneuron signaling either sex. Thus, might represent promising therapeutic target for brain disorders related excitation imbalance cortex. SIGNIFICANCE STATEMENT CCK, most abundant widely distributed neuropeptide CNS, colocalizes many neurotransmitters modulators. is one important neurotransmitters, much evidence shows that may be involved modulating areas. However, role CCK-GABA microcircuits still unclear. identified GPR173, localized synapses mediated effect,