Central amygdala somatostatin neurons modulate stress-induced sleep-onset insomnia

作者：Wei Yao, Shu-Xin Huang, Lei Zhang, Zhang-Shu Li, Ding-Yuan Huang, Kaiqi Huang, Zixuan Huang, Lei‐Lei Nian, Jialu Li, Li Chen, Ping Cai · 发表于：Communications Biology · 年份：2025 · DOI：10.1038/s42003-025-07679-8 · 被引用次数：8 · 研究领域：Sleep and Wakefulness Research、Circadian rhythm and melatonin、Photoreceptor and optogenetics research

Sleep-onset insomnia, characterized by difficulty falling asleep, is linked to increased health risks. Previous studies have shown that the central amygdala (CeA) plays a crucial role in stress regulation, with the somatostatin neurons in the CeA (CeASST+) involved in adaptive stress responses. However, the role of CeASST+ neurons in stress-induced sleep-onset insomnia remains unclear. In this study, we found that the activity of CeASST+ neurons is closely associated with stressful events using fiber photometry in mice. Acute optogenetic activation of CeASST+ neurons induced a rapid transition from non-rapid eye movement (NREM) sleep to wakefulness. Semi-chronic optogenetic and chemogenetic activation of CeASST+ neurons led to prolonged sleep-onset latency and increased wakefulness. Chemogenetic inhibition of these neurons ameliorated sleep-onset insomnia induced by stressful stimuli, but did not affect sleep-wake behavior under physiological conditions. Collectively, our results suggested that CeASST+ neurons are a key neural substrate for modulating stress-induced sleep-onset insomnia, without influencing physiological sleep. These findings highlight CeASST+ neurons as a promising target for treating stress-related sleep-onset insomnia in clinical practice. The sleep data from acute stress models indicate that CeA somatostatin neurons are a key neural substrate for modulating stress-induced sleep-onset insomnia, without influencing physiological sleep.