Nucleus accumbens neurons expressing dopamine D1 receptors modulate states of consciousness in sevoflurane anesthesia.

Although general anesthesia (GA) enables patients to undergo surgery without consciousness, the precise neural mechanisms underlying this phenomenon have yet to be identified. In addition to many studies over the past two decades implicating the thalamus, cortex, brainstem, and conventional sleep-wake circuits in GA-induced loss of consciousness (LOC), some recent studies have begun to highlight the importance of other brain areas as well. Here, we found that population activities of neurons expressing dopamine D1 receptor (D1R) in the nucleus accumbens (NAc), a critical interface between the basal ganglia and limbic system, began to decrease before sevoflurane-induced LOC and gradually returned after recovery of consciousness (ROC). Chemogenetic activation of NAcD1R neurons delayed induction of and accelerated emergence from sevoflurane GA, whereas chemogenetic inhibition of NAcD1R neurons exerted opposite effects. Moreover, transient activation of NAcD1R neurons induced significant cortical activation and behavioral emergence during continuous steady-state GA with sevoflurane or deep anesthesia state with constant and stable burst-suppression oscillations. Taken together, our findings uncover that NAcD1R neurons modulated states of consciousness associated with sevoflurane GA and may represent an area for targeting GA-induced changes in consciousness and ameliorating related adverse effects.