Lateral hypothalamus orexinergic inputs to lateral habenula modulate maladaptation after social defeat stress.
Lateral hypothalamus orexinergic inputs to lateral habenula modulate maladaptation after social defeat stress.
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下丘脑外侧的食欲素能输入对外侧缰核调节社交失败压力后的适应不良
DOI：
10.1016/j.ynstr.2021.100298
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发表时间：
2021-05
影响因子：
5
通讯作者：
Yang Q
中科院分区：
文献类型：
--
作者：
Wang D;Li A;Dong K;Li H;Guo Y;Zhang X;Cai M;Li H;Zhao G;Yang Q
社会应激是一种常见的应激源，它会导致多种形式的身心功能障碍。长期暴露于社会压力与心理障碍的风险较高有关，包括焦虑症和重度抑郁症（MDD）。食欲素能系统参与多种动机行为的调节。本研究旨在探讨下丘脑外侧区（LHA）至外侧缰核（LHb）的食欲素能投射在慢性社会失败应激后抑郁和焦虑样行为中的调节作用。当小鼠在社会互动过程中被击败时，LHA中的食欲素能神经元和LHb中的食欲素能神经元都被强烈激活，如FosTRAP策略所示。在LHb中注入食欲素显著减轻了由慢性社会失败压力引起的社会回避和抑郁样行为。在LHb中给予食欲素受体2拮抗剂进一步加重了抑郁表型。光激活食欲素能细胞体在LHA或终端在LHb缓解焦虑样行为引起的慢性社会失败的压力。总的来说，我们确定了抗抑郁和抗焦虑作用的回路从LHA食欲素能神经元的LHb在慢性社会压力的反应，提供了新的证据LHA食欲素电路的抗抑郁特性。
Social stress, a common stressor, causes multiple forms of physical and mental dysfunction. Prolonged exposure to social stress is associated with a higher risk of psychological disorders, including anxiety disorders and major depressive disorder (MDD). The orexinergic system is involved in the regulation of multiple motivated behaviors. The current study examined the regulatory effect of orexinergic projections from the lateral hypothalamic area (LHA) to the lateral habenula (LHb) in depression- and anxiety-like behaviors after chronic social defeat stress. When mice were defeated during social interaction, both orexinergic neurons in the LHA and glutamatergic neurons in the LHb were strongly activated, as indicated by the FosTRAP strategy. Infusion of orexin in the LHb significantly alleviated social avoidance and depression-like behaviors induced by chronic social defeat stress. Administration of an orexin receptor 2 antagonist in the LHb further aggravated the depressive phenotype. Photoactivation of orexinergic cell bodies in the LHA or terminals in the LHb relieved anxiety-like behaviors induced by chronic social defeat stress. Collectively, we identified the antidepressant and anxiolytic effects of the circuit from LHA orexinergic neurons to the LHb in response to chronic social stress, providing new evidence of the antidepressant properties of LHA orexin circuits.
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