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

• Published in: Biomedicine & pharmacotherapy Vol. 176; p. 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: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.07.2024; Elsevier
• Subjects: 5-hydroxytryptamine; Anesthetics, Inhalation - pharmacology; Animals; Basolateral amygdala; Basolateral Nuclear Complex - drug effects; Basolateral Nuclear Complex - metabolism; Basolateral Nuclear Complex - physiology; Consciousness; Consciousness - drug effects; Dorsal raphe nucleus; Dorsal Raphe Nucleus - drug effects; Dorsal Raphe Nucleus - metabolism; General anesthesia; Male; Mice; Mice, Inbred C57BL; Neural Pathways - drug effects; Neural Pathways - physiology; Optogenetics; Receptor, Serotonin, 5-HT1A - metabolism; Serotonin - metabolism; Sevoflurane; Sevoflurane - pharmacology; Sevoflurane; Basolateral amygdala; General anesthesia; Consciousness; 5-hydroxytryptamine; Dorsal raphe nucleus
• ISSN: 0753-3322; 1950-6007; 1950-6007
• DOI: 10.1016/j.biopha.2024.116937

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.