Neuronal Properties in the Lateral Habenula and Adult–Newborn Interactions in Virgin Female and Male Mice

The behavioral interactions between adults and newborns are decisive for the fitness and the survival of offspring across the animal kingdom. In laboratory mice, while virgin females display caregiving behaviors, virgin males are rather neglectful or aggressive toward pups. Despite the importance of these behavioral variations, the underlying neural mechanisms remain poorly understood. Brain regions encoding these behaviors may exhibit sex-dependent functional differences at the baseline. Additionally, these structures might undergo sex-specific plasticity after adults interact with the offspring. Emerging evidence suggests sex-based differences in input connectivity, genetics, and receptor expression of the epithalamic lateral habenula (LHb). Moreover, LHb neuronal activity is instrumental for adult-newborn interactions. However, whether LHb neuronal function varies between sexes and/or undergoes adaptations following interactions with pups has not been fully investigated. In this study, we used in vivo and ex vivo single-cell electrophysiology to examine the basal LHb neuronal activity of virgin female and male mice. In a second set of experiments, we exposed mice to pups and recapitulated sex-based divergent behaviors. Recordings in acute slices showed no alterations in LHb firing properties, regardless of sex or pup exposure. These findings suggest that, although the LHb participates in adult behaviors toward pups, this is not mediated by sex-dependent functional differences or adaptations in the neuronal firing properties. Thus, this study provides new insights into the neural basis of sex-specific adult-newborn behaviors and the role of the LHb in these processes.