A Sexually Dimorphic Neuronal Cluster in the Mouse Medial Amygdala Exhibits Binary Activation Mode Based on Male Sexual Status

Increasing scientific interest has been directed toward understanding sexual dimorphism in the brain. Although various brain structures exhibit masculine or feminine characteristics, no strictly binary anatomical feature, such as those seen in genitalia. has been identified. In this study, we identified a dense, sexually dimorphic cluster of neurons in the posterodorsal medial amygdala (MeApd), which we named DIMPLE, that exhibited a remarkable binary pattern of cFos activation. Using the TRAP2 (Targeted Recombination in Active Populations) transgenic mouse model, we found that it was consistently labeled in all females, regardless of age or sexual experience. In males, however, DIMPLE was not labeled in any of the adult virgins but was evident pre-weaning and following mating. Surgical removal of gonads (ovariectomy or orchiectomy) did not alter the labeling pattern of DIMPLE in either sex. Interestingly, a single intraperitoneal injection of prolactin, a hormone known to increase in males after mating, induced DIMPLE labeling in virgin males. However, treatment with cabergoline, a potent inhibitor of prolactin secretion, did not prevent DIMPLE labeling in females or in post-mating males. Given the established role of the MeApd in social and reproductive behaviors, we propose that DIMPLE may support neural mechanisms underlying female-typical behavior and potentially contribute to post-mating behavioral shifts in males. Abstract Figure Graphical abstract: Summary of DIMPLE activity during puberty and sexual status.