The thalamic reticular nucleus-lateral habenula circuit regulates depressive-like behaviors in chronic stress and chronic pain
Xin-Yue Wang,
Xiang Xu,
Rui Chen,
Wen-Bin Jia,
Peng-Fei Xu,
Xiao-Qing Liu,
Ying Zhang,
Xin-Feng Liu,
Yan Zhang
Affiliations
Xin-Yue Wang
Department of Neurology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
Xiang Xu
Department of Neurology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
Rui Chen
Department of Neurology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
Wen-Bin Jia
Department of Neurology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
Peng-Fei Xu
Department of Neurology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
Xiao-Qing Liu
School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China
Ying Zhang
Neuroscience Research Institute, Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory for Neuroscience, Ministry of Education/National Health Commission of China, Peking University, Beijing 100191, China; Corresponding author
Xin-Feng Liu
Department of Neurology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China; Corresponding author
Yan Zhang
Department of Neurology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China; Corresponding author
Summary: Chronic stress and chronic pain are two major predisposing factors to trigger depression. Enhanced excitatory input to the lateral habenula (LHb) has been implicated in the pathophysiology of depression. However, the contribution of inhibitory transmission remains unclear. Here, we dissect an inhibitory projection from the sensory thalamic reticular nucleus (sTRN) to the LHb, which is activated by acute aversive stimuli. However, chronic restraint stress (CRS) weakens sTRN-LHb synaptic strength, and this synaptic attenuation is indispensable for CRS-induced LHb neural hyperactivity and depression onset. Moreover, artificially inhibiting the sTRN-LHb circuit induces depressive-like behaviors in healthy mice, while enhancing this circuit relieves depression induced by both chronic stress and chronic pain. Intriguingly, neither neuropathic pain nor comorbid mechanical hypersensitivity in chronic stress is affected by this pathway. Altogether, our study demonstrates an sTRN-LHb circuit in establishing and modulating depression, thus shedding light on potential therapeutic targets for preventing or managing depression.
