Dorsal raphe nucleus to basolateral amygdala 5-HTergic neural circuit modulates restoration of consciousness during sevoflurane anesthesia

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-arou...

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Bibliographic Details
Published in:Biomedicine & pharmacotherapy 2024-07, Vol.176, p.116937, Article 116937
Main Authors: Yu, Qian, Wang, YuLing, Gu, LeYuan, Shao, WeiHui, Gu, JiaXuan, Liu, Lu, Lian, XiTing, Xu, Qing, Zhang, YuanLi, Yang, Yue, Zhang, ZhuoYue, Wu, YaXuan, Ma, HaiXiang, Shen, Yue, Ye, Wen, Wu, YanHui, Yang, HuiFang, Chen, LiHai, Nagayasu, Kazuki, Zhang, HongHai
Format: Article
Language:English
Subjects:
5-hydroxytryptamine
Basolateral amygdala
Consciousness
Dorsal raphe nucleus
General anesthesia
Sevoflurane
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Summary: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. [Display omitted] •Activation of DR-BLA 5-HTergic neural circuit facilitates recovery of consciousness from sevoflurane anesthesia.•5-HT1A receptors are critical for regulating anesthetic arousal.•5-hydroxytryptophan may be a promising candidate for preventing delayed recovery.
ISSN:0753-3322
1950-6007
1950-6007
DOI:10.1016/j.biopha.2024.116937