Department of Anesthesiology, the Fourth Clinical School of Medicine, Zhejiang Chinese Medical University, Hangzhou 310006, China; Department of Anesthesiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
Department of Anesthesiology, the Fourth Clinical School of Medicine, Zhejiang Chinese Medical University, Hangzhou 310006, China.
Biomed Pharmacother. 2024 Jul;176:116937. doi: 10.1016/j.biopha.2024.116937. Epub 2024 Jun 12.
The advent of general anesthesia (GA) has significant implications for clinical practice. However, the exact mechanisms underlying GA-induced transitions in consciousness remain elusive. Given some similarities between GA and sleep, the sleep-arousal neural nuclei and circuits involved in sleep-arousal, including the 5-HTergic system, could be implicated in GA. Herein, we utilized pharmacology, optogenetics, chemogenetics, fiber photometry, and retrograde tracing to demonstrate that both endogenous and exogenous activation of the 5-HTergic neural circuit between the dorsal raphe nucleus (DR) and basolateral amygdala (BLA) promotes arousal and facilitates recovery of consciousness from sevoflurane anesthesia. Notably, the 5-HT1A receptor within this pathway holds a pivotal role. Our findings will be conducive to substantially expanding our comprehension of the neural circuit mechanisms underlying sevoflurane anesthesia and provide a potential target for modulating consciousness, ultimately leading to a reduction in anesthetic dose requirements and side effects.
全身麻醉(GA)的出现对临床实践具有重要意义。然而,GA 诱导意识转变的确切机制仍难以捉摸。鉴于 GA 和睡眠之间存在一些相似之处,涉及睡眠-觉醒的睡眠-觉醒神经核和回路,包括 5-羟色胺能系统,可能与 GA 有关。在此,我们利用药理学、光遗传学、化学遗传学、光纤光度法和逆行追踪技术来证明背侧中缝核(DR)和基底外侧杏仁核(BLA)之间的内源性和外源性 5-羟色胺能神经回路的激活均可促进觉醒,并有助于从七氟醚麻醉中恢复意识。值得注意的是,该通路中的 5-HT1A 受体起着关键作用。我们的发现将有助于极大地扩展我们对七氟醚麻醉的神经回路机制的理解,并为调节意识提供一个潜在的靶点,最终减少麻醉剂量需求和副作用。