Abstract:
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.
摘要:
全身麻醉(GA)的出现对临床实践具有重要意义。然而,GA诱导的意识转变的确切机制仍然难以捉摸。考虑到GA和睡眠之间的一些相似之处,参与睡眠唤醒的睡眠唤醒神经核和回路,包括5-HTergic系统,可能与GA有关。在这里,我们利用药理学,光遗传学,化学遗传学,纤维测光,和逆行追踪表明,背侧中缝核(DR)和基底外侧杏仁核(BLA)之间的5-HTergic神经回路的内源性和外源性激活均可促进七氟醚麻醉后的唤醒并促进意识恢复。值得注意的是,5-HT1A受体在该途径中具有关键作用。我们的发现将有助于大大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目标。最终导致麻醉剂量需求和副作用的减少。