GABAergic neurons in the Nucleus Accumbens are involved in the general anesthesia effect of propofol

Introduction: The mechanism by which general anesthetic drugs modify the state of consciousness remains unidentified. In essence, the Nucleus Accumbens(NAc)may be directly engaged in the principle of general anesthesia. However, it is uncertain whether NAc GABAergic neurons play a role in the propofol-induced general anesthesia effect.

Methods: We used immunofluorescence and Western blotting to access the activities of NAc GABAergic neurons during propofol anesthesia, and then we utilized chemogenetic and optogenetic methods to investigate the necessity of NAc GABAergic neurons in the change of consciousness. Moreover, we also conducted behavioral tests to analyze anesthetic induction and emergence.

Results: We found out that c-Fos expression was considerably dropped in NAc GABAergic neurons after propofol injection. Notably, chemically selective stimulation of NAc GABAergic neurons during propofol anesthesia lowered propofol sensitivity, prolonged the induction of propofol anesthesia, and facilitated recovery; the inhibition of NAc GABAergic neurons exerted opposite effects. Furthermore, optogenetic activation of NAc GABAergic neurons promoted emergence whereas the result of optogenetic inhibition was the opposite.

Conclusions: Our results demonstrate that NAc GABAergic neurons modulate induction and emergence of propofol anesthesia.