Volume 38, Issue 7, 2022


Sex differences in response to general anesthesia have been reported previously, but the underlying neural mechanism remained unknown. In the current study, male mice were confirmed to be more sensitive to sevoflurane than females. This sex difference was mediated by estrogen receptor α (ERα) on GABAergic neurons in the medical preoptic area (MPA) of males. ERα signaling stimulated the GABAergic MPA neurons in males but had no effect on that in females. The activation of GABAergic neurons exerted an inhibitory effect on neural networks that, in turn, facilitated the anesthesia process. In the cover image, the female mouse is fighting against sevoflurane anesthesia, while the male mouse has already fallen asleep. In the brain, ERα has ignited the MPA GABAergic neurons in the male mouse, but in the female, the GABAergic neurons keep silent. See pages 703–719. (Cover provided by Dr. Hailong Dong).