Emotional disorders, such as anxiety and depression, represent a major societal problem; however, the underlying neurological mechanism remains unknown. The ventral lateral septum (LSv) is implicated in regulating processes related to mood and motivation. In this study, we found that LSv GABAergic neurons were significantly activated in mice experiencing chronic social defeat stress (CSDS) after exposure to a social stressor. We then controlled LSv GABAergic neuron activity using a chemogenetic approach. The results showed that although manipulation of LSv GABAergic neurons had little effect on anxiety-like behavioral performances, the activation of LSv GABAergic neurons during CSDS worsened social anxiety during a social interaction (SI) test. Moreover, LSv GABAergic neurons showed strong projections to the paraventricular nucleus (PVN) of the hypothalamus, which is a central hub for stress reactions. Remarkably, while activation of GABAergic LSv–PVN projections induced social anxiety under basal conditions, activation of this pathway during CSDS alleviated social anxiety during the SI test. On the other hand, the chemogenetic manipulation of LSv GABAergic neurons or LSvGABA–PVN projections had no significant effect on despair-like behavioral performance in the tail suspension test. Overall, LS GABAergic neurons, particularly the LSv GABAergic–PVN circuit, has a regulatory role in pathological anxiety and is thus a potential therapeutic target for the treatment of emotional disorders.

中文翻译：

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从腹侧外侧隔膜到下丘脑室旁核的 GABA 能突触调节焦虑

情绪障碍，例如焦虑和抑郁，是一个主要的社会问题；然而，潜在的神经机制仍然未知。腹侧外侧隔膜（LSv）参与与情绪和动机相关的调节过程。在这项研究中，我们发现在暴露于社交压力源后经历慢性社交挫败压力（CSDS）的小鼠中，LSv GABA 能神经元显着激活。然后，我们使用化学遗传学方法控制 LSv GABA 能神经元活动。结果表明，虽然操纵 LSv GABA 能神经元对类焦虑行为表现影响不大，但在 CSDS 期间激活 LSv GABA 能神经元会加剧社交互动 (SI) 测试中的社交焦虑。此外，LSv GABA能神经元对下丘脑的室旁核（PVN）表现出强烈的投射，而室旁核是应激反应的中枢。值得注意的是，虽然 GABA 能 LSv-PVN 投射的激活会在基础条件下引起社交焦虑，但在 CSDS 期间激活该通路可减轻 SI 测试期间的社交焦虑。另一方面，LSv GABA 能神经元或 LSv 的化学遗传学操作氨基丁酸–PVN 预测对尾部悬挂测试中的绝望行为表现没有显着影响。总体而言，LS GABA能神经元，特别是LSv GABA能-PVN回路，在病理性焦虑中具有调节作用，因此是治疗情绪障碍的潜在治疗靶点。