Zhu Yuxuan, Wu Tongrui, Jiao Qingyan, Chai Haitong, Wang Yuang, Tian Chunxiao, Xue Qiuying, Li Kai, Wang Pu, Li Zibing, He Hualin, Chen Bo, Liu Aili, Shen Hui
Laboratory of Neurobiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Laboratory of Neurobiology, School of Biomedical Engineering, Tianjin Medical University, Tianjin, China.
Sci Adv. 2025 Sep 12;11(37):eadx2666. doi: 10.1126/sciadv.adx2666. Epub 2025 Sep 10.
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.
急性睡眠剥夺（SD）能迅速缓解抑郁，填补了情绪障碍治疗中的一个关键空白。快速眼动睡眠剥夺（REM SD）可调节血管活性肠肽（VIP）神经元的兴奋性，影响锥体神经元的突触可塑性。然而，确切机制仍不明确。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，特别针对内侧前额叶皮质（mPFC）中的VIP神经元。我们的结果表明，REM SD通过抑制VIP神经元活动减轻抑郁，这直接增加了锥体神经元的兴奋性，从而促进突触可塑性恢复。此外，mPFC锥体神经元上VPAC2的敲低表明，这些神经元中VPAC2介导的AC/cAMP/PKA信号通路对于REM SD减轻抑郁样行为至关重要。这些发现表明，VIP神经元直接调节锥体神经元，并且在REM SD减轻抑郁方面起着关键作用。
