Hypothalamic corticotropin-releasing hormone neurons modulate sevoflurane anesthesia and the post-anesthesia stress...

General anesthesia (GA) is an indispensable procedure necessary for safely and compassionately administering a significant number of surgical procedures and invasive diagnostic tests. However, the undesired stress response associated with GA causes delayed recovery and even increased morbidity in the clinic. Here, a core hypothalamic ensemble, corticotropin-releasing hormone neurons in the paraventricular nucleus of the hypothalamus (PVH^CRH neurons), is discovered to play a role in regulating sevoflurane GA. Chemogenetic activation of these neurons delay the induction of and accelerated emergence from sevoflurane GA, whereas chemogenetic inhibition of PVH^CRH neurons accelerates induction and delays awakening. Moreover, optogenetic stimulation of PVH^CRH neurons induce rapid cortical activation during both the steady and deep sevoflurane GA state with burst-suppression oscillations. Interestingly, chemogenetic inhibition of PVH^CRH neurons relieve the sevoflurane GA-elicited stress response (e.g., excessive self-grooming and elevated corticosterone level). These findings identify PVH^CRH neurons modulate states of anesthesia in sevoflurane GA, being a part of anesthesia regulatory network of sevoflurane.