Potentiation of the lateral habenula-ventral tegmental area pathway underlines the susceptibility to depression in mice with chronic pain  

作　　者：Chun-Kui Zhang Pan Wang Yuan-Yuan Ji Jian-Shuai Zhao Jun-Xiang Gu Xian-Xia Yan Hong-Wei Fan Ming-Ming Zhang Yu Qiao Xiao-Die Liu Bao-Juan Li Ming-Hui Wang Hai-Long Dong Hao-Hong Li Peng-Cheng Huang Yun-Qing Li Wu-Gang Hou Jin-Lian Li Tao Chen 

机构地区：[1]Department of Anatomy and K.K.Leung Brain Research Centre,Fourth Military Medical University,Xi’an 710032,China [2]Beijing Institute of Basic Medical Sciences,Beijing 100850,China [3]Key Laboratory of Ministry of Public Health for Forensic Science,Xi’an Jiaotong University,Xi’an 710061,China [4]Department of Anesthesiology,Xijing Hospital,Fourth Military Medical University,Xi’an 710032,China [5]Department of Neurosurgery,the Second Affiliated Hospital of Xian Jiaotong University,Xi’an 710004,China [6]School of Biomedical Engineering,Fourth Military Medical University,Xi’an 710032,China [7]Affiliated Mental Health Centre and Hangzhou Seventh People’s Hospital,Zhejiang University School of Medicine,Hangzhou 310013,China [8]The MOE Frontier Research Center of Brain&Brain-machine Integration,Zhejiang University School of Brain Science and Brain Medicine,Hangzhou 310058,China [9]Department of Neurology,The First Affiliated Hospital of Nanchang University,Nanchang 330006,China [10]Department of Anatomy,School of Medicine,Northwest University,Xi’an 710069,China

出　　处：《Science China(Life Sciences)》2024年第1期67-82,共16页中国科学（生命科学英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(32192410,32071000,81870866,81571074,82230037,81971226,81620108008,82130034);the Foundation for Distinguished Young Scholars of ShaanXi(2019JC-21,2021JC-33);Young Scholar Project of the First Affiliated Hospital of Nanchang University(YFYPY202109);the Boost Plan of Xijing Hospital(XJZT21J01).

摘　　要：Chronic pain often develops severe mood changes such as depression.However,how chronic pain leads to depression remains elusive and the mechanisms determining individuals’responses to depression are largely unexplored.Here we found that depression-like behaviors could only be observed in 67.9%of mice with chronic neuropathic pain,leaving 32.1%of mice with depression resilience.We determined that the spike discharges of the ventral tegmental area(VTA)-projecting lateral habenula(LHb)glutamatergic(Glu)neurons were sequentially increased in sham,resilient and susceptible mice,which consequently inhibited VTA dopaminergic(DA)neurons through a LHbGlu-VTAGABA-VTADA circuit.Furthermore,the LHbGlu-VTADA excitatory inputs were dampened via GABAB receptors in a pre-synaptic manner.Regulation of LHb-VTA pathway largely affected the development of depressive symptoms caused by chronic pain.Our study thus identifies a pivotal role of the LHb-VTA pathway in coupling chronic pain with depression and highlights the activity-dependent contribution of LHbGlu-to-VTADA inhibition in depressive behavioral regulation.

关 键 词：chronic pain DEPRESSION lateral habenula ventral tegmental area DOPAMINE SUSCEPTIBILITY 

分 类 号：R402[医药卫生—临床医学]