Central nucleus of the amygdala to medial prefrontal cortex 5-HTergic neural circuit modulates the recovery of consciousness during sevoflurane anesthesia

General anesthesia, widely employed for its capacity to induce unconsciousness during surgical and diagnostic procedures, frequently results in postoperative recovery delays, a common complication. The precise mechanisms underpinning this delayed emergence from anesthesia remain not fully understood. Prior research has established a strong association between sleep-wake neural circuits and the anesthetic effects of general anesthetics, with serotonin (5-HT) playing a pivotal role in the regulation of anesthesia emergence. Extensive projections exist between the amygdala and the medial prefrontal cortex (mPFC). In this study, we utilized pharmacological, chemogenetic, and optogenetic techniques to explore the relationship between the 5-HT neural circuitry within the central amygdala (CeA)-mPFC pathway and the process of awakening from general anesthesia. Our findings reveal that modulating the 5-HT system in both the CeA and mPFC, via endogenous and exogenous means, can effectively reverse delayed emergence. This suggests that the 5-HT-ergic pathway within the CeA-mPFC circuit is instrumental in regulating the awakening process from sevoflurane anesthesia. These insights may inform future clinical interventions designed to prevent delayed emergence and reduce postoperative risks.