Hypothalamic CRH Neurons Modulate Sevoflurane Anesthesia and The Post-anesthesia Stress Responses

General anesthesia 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 general anesthesia (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^CRHneurons), 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^CRHneurons accelerates induction and delays awakening. Moreover, optogenetic stimulation of PVH^CRHneurons induce rapid cortical activation during both the steady and deep sevoflurane GA state with burst-suppression oscillations. Interestingly, chemogenetic inhibition of PVH^CRHneurons relieve the sevoflurane GA-elicited stress response (e.g., excessive self-grooming and elevated corticosterone level). These findings identify PVH^CRHneurons modulate states of anesthesia in sevoflurane GA, being a part of anesthesia regulatory network of sevoflurane.