Behavioral Transition from Attack to Parenting in Male Mice: A Crucial Role of the Vomeronasal System

<jats:p>Sexually naive male mice show robust aggressive behavior toward pups. However, the proportion of male mice exhibiting pup-directed aggression declines after cohabitation with a pregnant female for 2 weeks after mating. Subsequently, on becoming fathers, they show parental behavior toward pups, similar to maternal behavior by mothers. To elucidate the neural mechanisms underlying this behavioral transition, we examined brain regions differentially activated in sexually naive males and fathers after exposure to pups, using c-Fos expression as a neuronal activation marker. We found that, after pup exposure, subsets of neurons along the vomeronasal neural pathway—including the vomeronasal sensory neurons, the accessory olfactory bulb, the posterior medial amygdala, the medioposterior division of the bed nucleus of stria terminalis, and the anterior hypothalamic area—were more strongly activated in sexually naive males than in fathers. Notably, c-Fos induction was not observed in the vomeronasal sensory neurons of fathers after pup exposure. Surgical ablation of the vomeronasal organ in sexually naive males resulted in the abrogation of pup-directed aggression and simultaneous induction of parental behavior. These results suggest that chemical cues evoking pup-directed aggression are received by the vomeronasal sensory neurons and activate the vomeronasal neural pathway in sexually naive male mice but not in fathers. Thus, the downregulation of pup pheromone-induced activation of the vomeronasal system might be important for the behavioral transition from attack to parenting in male mice.</jats:p>