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

Abstract

General anesthetics benefit patients undergoing surgeries without consciousness, but 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 (PVHCRH neurons) is discovered, which regulates the anesthetic effects and post-anesthesia stress response of sevoflurane GA. Chemogenetic activation of these neurons delay the induction of and accelerated emergence from sevoflurane GA, whereas chemogenetic inhibition exert the opposite effects. Moreover, optogenetic stimulation of PVHCRH neurons induce rapid cortical activation during both the steady and deep sevoflurane GA state with burst-suppression oscillations. Interestingly, chemogenetic inhibition of PVHCRH neurons relieve the sevoflurane GA-elicited stress response (e.g., excessive self-grooming and elevated corticosterone level). These findings identify a common neural substrate integrating the anesthetic effect and post-anesthesia stress response of sevoflurane GA.