Single-neuron projectome-guided analysis reveals the neural circuit mechanism underlying endogenous opioid antinociception  

作　　者：Yan-Nong Dou Yuan Liu Wen-Qun Ding Qing Li Hua Zhou Ling Li Meng-Ting Zhao Zheng-Yi-Qi Li Jing Yuan Xiao-Fei Wang Wang-Yuan Zou Anan Li Yan-Gang Sun 

机构地区：[1]Institute of Neuroscience,Key Laboratory of Brain Cognition and Brain-Inspired Intelligence Technology,CAS Center for Excellencein Brain Science&Intelligence Technology,Chinese Academy of Sciences,Shanghai 200031,China [2]Department of Biology,School of Life Science and Technology,Shanghai Tech University,Shanghai 201210,China [3]Lingang Laboratory,Shanghai 200031,China [4]University of Chinese Academy of Sciences,Beijing 100049,China [5]Britton Chance Center for Biomedical Photonics,Wuhan National Laboratory for Optoelectronics,MoE Key Laboratory for Biomedical Photonics,Huazhong University of Scienceand Technology,Wuhan 430074,China [6]Department of Anesthesiology,Xiangya Hospital,Central South University,Changsha 410008,China [7]HUST-Suzhou Institute for Brainsmatics,JITRI,Suzhou 215123,China

出　　处：《National Science Review》2024年第7期100-119,共20页国家科学评论（英文版）

基　　金：supported by the National Science and Technology Innovation 2030 Major Program(2021ZD0204404);the National Natural Science Foundation of China(82271244,32221003);the Shanghai Municipal Science and Technology Major Project(2018SHZDZX05);the YangFan project(21YF1453200);supported by the Youth Innovation Promotion Association,Chinese Academy of Sciences(2022266);supported by New Cornerstone Science Foundation through the Xplorer prize.

摘　　要：Endogenous opioid antinociception is a self-regulatory mechanism that reduces chronic pain,but its underlying circuit mechanism remains largely unknown.Here,we showed that endogenous opioid antinociception required the activation of mu-opioid receptors(MORs)in GABAergic neurons of the central amygdala nucleus(CEA)in a persistent-hyperalgesia mouse model.Pharmacogenetic suppression of these CEAMOR neurons,which mimics the effect of MOR activation,alleviated the persistent hyperalgesia.Furthermore,single-neuron projection analysis revealed multiple projectome-based subtypes of CEAMOR neurons,each innervating distinct target brain regions.We found that the suppression of axon branches projecting to the parabrachial nucleus(PB)of one subtype of CEAMOR neurons alleviated persistent hyperalgesia,indicating a subtype-and axonal-branch-specific mechanism of action.Further electrophysiological analysis revealed that suppression of a distinct CEA-PB disinhibitory circuit controlled endogenous opioid antinociception.Thus,this study identified the central neural circuit that underlies endogenous opioid antinociception,providing new insight into the endogenous pain modulatory mechanisms.

关 键 词：endogenous opioid antinociception mu-opioid receptors central amygdala nucleus parabrachial nucleus single-neuron projectome 

分 类 号：Q41[生物学—生理学]