睡眠-觉醒和麻醉-苏醒的神经环路机制仍旧没有得到完整的解析。终纹床核（the bed nucleus of the stria terminalis, BNST）中γ-氨基丁酸（γ-aminobutyric acid, GABA）能神经元在压力、恐惧等依赖高度觉醒的行为中起着至关重要。然而，目前尚不清楚BNST GABA能神经元是否能直接参与睡眠觉醒和麻醉苏醒的调节。
2024年3月19日，重庆脑与智能科学中心记忆原理研究部与重庆大学附属肿瘤医院刘红亮/肖静宇团队、广西大学等合作，在Communications Biology期刊上发表学术论文“BNST GABAergic neurons modulate wakefulness over sleep and anesthesia”，揭示了BNST GABA能神经元在觉醒调控的作用及机制。
研究人员首先联合使用光纤光度法，脑电图、肌电图监测和行为学记录，发现BNST GABA能神经元钙活动伴随觉醒而显著升高，并在清醒和快速眼动睡眠时期活动较高，在麻醉时活动降低。光遗传激活BNST GABA能神经元能够诱发小鼠从非快速眼动睡眠和快速眼动睡眠到觉醒的快速转换，长时程光遗传激活BNST GABA能神经元可以维持觉醒状态。对BNST GABA能神经元的慢性损伤实验发现，损伤后会引起小鼠夜间睡眠结构的改变，而对麻醉过程中的诱导和唤醒过程没有显著影响。此外，我们还发现BNST -腹侧被盖区通路参与了这一促觉醒的功能。
图1. BNST GABA能神经元在自然睡眠觉醒周期中的活动模式
图2. 激活BNST GABA能神经元具有促进觉醒作用综上所述，本研究结果表明BNST GABA能神经元在促觉醒和麻醉苏醒中发挥作用，揭示了睡眠觉醒和麻醉背后的新神经环路机制，这将为意识的解读以及麻醉剂的创新发展提供新思路。该工作由国家自然科学基金等资助完成。
Abstract
The neural circuits underlying sleep-wakefulness and general anesthesia have not been fully investigated. The GABAergic neurons in the bed nucleus of the stria terminalis (BNST) play a critical role in stress and fear that relied on heightened arousal. Nevertheless, it remains unclear whether BNST GABAergic neurons are involved in the regulation of sleep-wakefulness and anesthesia. Here, using in vivo fiber photometry combined with electroencephalography, electromyography, and video recordings, we found that BNST GABAergic neurons exhibited arousal-state-dependent alterations, with high activities in both wakefulness and rapid-eye movement sleep, but suppressed during anesthesia. Optogenetic activation of these neurons could initiate and maintain wakefulness, and even induce arousal from anesthesia. However, chronic lesion of BNST GABAergic neurons altered spontaneous sleep-wakefulness architecture during the dark phase, but not induction and emergence from anesthesia. Furthermore, we also discovered that the BNST-ventral tegmental area pathway might participate in promoting wakefulness and reanimation from steady-state anesthesia. Collectively, our study explores new elements in neural circuit mechanisms underlying sleepwakefulness and anesthesia, which may contribute to a more comprehensive understanding of consciousness and the development of innovative anesthetics.
原文链接：
https://www.nature.com/articles/s42003-024-06028-5
参考文献
Li M, Li W, Liang S, et al. BNST GABAergic neurons modulate wakefulness over sleep and anesthesia. Commun Biol. 2024;7(1):339. Published 2024 Mar 19. doi:10.1038/s42003-024-06028-5
