Acute REM sleep deprivation alleviated depression-like behavior mediated by inhibiting VIP neurons in the mPFC

IF 12.5 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2025-09-10 DOI:10.1126/sciadv.adx2666

Yuxuan Zhu, Tongrui Wu, Qingyan Jiao, Haitong Chai, Yuang Wang, Chunxiao Tian, Qiuying Xue, Kai Li, Pu Wang, Zibing Li, Hualin He, Bo Chen, Aili Liu, Hui Shen

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Abstract

Acute sleep deprivation (SD) rapidly alleviates depression, addressing a critical gap in mood disorder treatment. Rapid eye movement SD (REM SD) modulates the excitability of vasoactive intestinal peptide (VIP) neurons, influencing the synaptic plasticity of pyramidal neurons. However, the precise mechanism remains undefined. To investigate this, we used a modified multiple platform method (MMPM) to induce 12 hours of REM SD, specifically targeting VIP neurons in the medial prefrontal cortex (mPFC). Our results show that REM SD mitigated depression by suppressing VIP neurons activity, which directly increased the excitability of pyramidal neurons and, consequently, promoted synaptic plasticity recovery. In addition, the knockdown of VPAC2 on mPFC pyramidal neurons revealed that VPAC2-mediated AC/cAMP/PKA signaling pathway in these neurons is essential for REM SD to mitigate depression-like behavior. These findings suggest that VIP neurons directly regulate pyramidal neurons and are crucial in alleviating depression by REM SD.

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急性快速眼动睡眠剥夺通过抑制mPFC VIP神经元减轻抑郁样行为

急性睡眠剥夺（SD）能迅速缓解抑郁症，填补了情绪障碍治疗的一个关键空白。快速眼动SD （REM SD）调节血管活性肠肽（VIP）神经元的兴奋性，影响锥体神经元的突触可塑性。然而，确切的机制仍然不清楚。为了研究这一点，我们使用改良的多平台方法（MMPM）诱导12小时的REM SD，专门针对内侧前额叶皮层（mPFC）的VIP神经元。我们的研究结果表明，REM SD通过抑制VIP神经元的活动来减轻抑郁，这直接增加了锥体神经元的兴奋性，从而促进了突触可塑性的恢复。此外，mPFC锥体神经元上VPAC2的下调表明，这些神经元中VPAC2介导的AC/cAMP/PKA信号通路对REM SD减轻抑郁样行为至关重要。这些发现提示VIP神经元直接调控锥体神经元，在REM SD缓解抑郁中起着重要作用。

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来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.