Deep brain stimulation in the lateral habenula reverses local neuronal hyperactivity and ameliorates depression-like behaviors in rats
Deep brain stimulation in the lateral habenula reverses local neuronal hyperactivity and ameliorates depression-like behaviors in rats
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DOI：
10.1016/j.nbd.2023.106069
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发表时间：
2023-03
影响因子：
6.1
通讯作者：
Yuqi Zhang;Longyu Ma;Xueying Zhang;Lupeng Yue;Jiaxin Wang;Jie Zheng;Shuang Cui;Fengyu Liu
中科院分区：
文献类型：
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作者：
Yuqi Zhang;Longyu Ma;Xueying Zhang;Lupeng Yue;Jiaxin Wang;Jie Zheng;Shuang Cui;Fengyu Liu
深部脑刺激（DBS）是治疗难治性抑郁症的一种有前景的疗法，但其治疗作用的机制仍不清楚。越来越多的证据表明，外侧缰核 (LHb) 与重度抑郁症之间存在密切关联，并表明 LHb 可能是 DBS 治疗抑郁症的有效靶点。在这里，我们发现，LHb 中的 DBS 有效地减少了经历慢性不可预测轻度应激 (CUMS) 的大鼠的抑郁样行为，CUMS 是啮齿类动物抑郁建模的一种广为接受的范例。体内电生理记录揭示了 CUMS 增加了神经元爆发放电，以及 LHb 中对厌恶刺激表现出过度活跃的神经元比例。尽管如此，DBS 下调了局部场电位功率，逆转了 CUMS 诱导的 LHb 爆发放电和神经元对厌恶刺激的过度活跃的增加，并降低了 LHb 和腹侧被盖区 (VTA) 之间的一致性。我们的结果表明，LHb 中的 DBS 具有抗抑郁样作用并逆转局部神经过度活跃，支持 LHb 作为 DBS 治疗抑郁症的目标。
Deep brain stimulation (DBS) is a promising therapy for treatment-resistant depression, while mechanisms underlying its therapeutic effects remain poorly defined. Increasing evidence has revealed an intimate association between the lateral habenula (LHb) and major depression, and suggests that the LHb might be an effective target of DBS therapy for depression. Here, we found that DBS in the LHb effectively decreased depression-like behaviors in rats experienced with chronic unpredictable mild stress (CUMS), a well-accepted paradigm for modeling depression in rodents.In vivoelectrophysiological recording unveiled that CUMS increased neuronal burst firing, as well as the proportion of neurons showing hyperactivity to aversive stimuli in the LHb. Nevertheless, DBS downregulated local field potential power, reversed the CUMS-induced increase of LHb burst firing and neuronal hyperactivity to aversive stimuli, and decreased the coherence between LHb and ventral tegmental area (VTA). Our results demonstrate that DBS in the LHb exerts antidepressant-like effects and reverses local neural hyperactivity, supporting the LHb as a target of DBS therapy for depression.