The thalamic reticular nucleus-lateral habenula circuit regulates depressive-like behaviors in chronic stress and chronic pain.
The thalamic reticular nucleus-lateral habenula circuit regulates depressive-like behaviors in chronic stress and chronic pain.
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DOI：
10.1016/j.celrep.2023.113170
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发表时间：
2023-09
期刊：
影响因子：
8.8
通讯作者：
Xinyue Wang;Xiang Xu;Ruifeng Chen;Wenda Jia;Pengfei Xu;Xiao-qing Liu;Y. Zhang;Xin-Feng Liu;Yan Zhang
中科院分区：
文献类型：
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作者：
Xinyue Wang;Xiang Xu;Ruifeng Chen;Wenda Jia;Pengfei Xu;Xiao-qing Liu;Y. Zhang;Xin-Feng Liu;Yan Zhang
慢性压力和慢性疼痛是引发抑郁症的两个主要诱发因素。外侧缰核（LHb）的兴奋性输入增强与抑郁症的病理生理学有关。然而，抑制性传递的贡献仍不清楚。在这里，我们解剖的抑制性投射从感觉丘脑网状核（sTRN）的LHb，这是激活急性厌恶刺激。然而，慢性束缚应激（CRS）削弱sTRN-LHb突触强度，这种突触衰减是CRS诱导的LHb神经活动过度和抑郁发作所必需的。此外，人工抑制sTRN-LHb回路在健康小鼠中诱导抑郁样行为，而增强该回路缓解由慢性应激和慢性疼痛诱导的抑郁。有趣的是，神经性疼痛和慢性应激中的共病机械超敏反应都不受此通路的影响。总之，我们的研究表明sTRN-LHb回路在建立和调节抑郁症中，从而揭示了预防或管理抑郁症的潜在治疗靶点。
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.