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

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外文摘要：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 se-quentially 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 con-tribution of LHbGlu-to-VTADA inhibition in depressive behavioral regulation.

外文关键词：

chronic paindepressionlateral habenulaventral tegmental areadopaminesusceptibility

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

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作者单位：

Department of Anatomy and K.K.Leung Brain Research Centre,Fourth Military Medical University,Xi'an 710032,China

Beijing Institute of Basic Medical Sciences,Beijing 100850,China

Key Laboratory of Ministry of Public Health for Forensic Science,Xi'an Jiaotong University,Xi'an 710061,China

Department of Anesthesiology,Xijing Hospital,Fourth Military Medical University,Xi'an 710032,China

Department of Neurosurgery,the Second Affiliated Hospital of Xian Jiaotong University,Xi'an 710004,China

School of Biomedical Engineering,Fourth Military Medical University,Xi'an 710032,China

Affiliated Mental Health Centre and Hangzhou Seventh People's Hospital,Zhejiang University School of Medicine,Hangzhou 310013,China

The MOE Frontier Research Center of Brain & Brain-machine Integration,Zhejiang University School of Brain Science and Brain Medicine,Hangzhou 310058,China

Department of Neurology,The First Affiliated Hospital of Nanchang University,Nanchang 330006,China

Department of Anatomy,School of Medicine,Northwest University,Xi'an 710069,China

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基金：

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaFoundation for Distinguished Young Scholars of ShaanXiFoundation for Distinguished Young Scholars of ShaanXiYoung Scholar Project of the First Affiliated Hospital of Nanchang UniversityBoost Plan of Xijing Hospital

项目编号：

32192410.320710008187086681571074.822300378197122681620108008821300342019JC-212021JC-33YFYPY202109XJZT21J01

出版年：

2024

DOI：

10.1007/s11427-023-2406-3

中国科学:生命科学(英文版)

中国科学院

中国科学:生命科学(英文版)

CSTPCD

影响因子：0.806

ISSN：1674-7305

年,卷(期)：2024.67(1)

参考文献量57