Olfactory cues and neural substrates driving infanticide in male mice

Infant mice emit chemical cues that trigger parental care in mothers and fathers but provoke aggression in unfamiliar virgin males. This aggressive behavior requires detection of these chemosignals by the vomeronasal organ, which transfers relevant information to olfactory-related brain regions. Despite our accumulating knowledge in the neurobiology of aggression, the identity of the chemosignals and neural mechanisms underlying this behavior remain poorly characterized. By combining Ca²? imaging and Egr1 expression analysis in vomeronasal neurons, we identified a set of nine pup-derived molecules that, when tested together, induce aggression in virgin males. In the brain, transcriptional profiling of aromatase-expressing (Aro+) neurons revealed a large-scale regulation of differential gene expression between fathers and virgin males within the medial amygdala. In this region, Aro+ neurons co-express the oxytocin receptor (OTR) and are activated by pup odors. We used two conditional disruption models to explore the role of OTR signaling in regulating infanticide in two cell types, targeting olfactory marker protein (Omp+)-expressing neurons of the olfactory periphery and Aro+ neurons. We observed that the Aro+ cell type, but not Omp+, is essential for pup-directed aggression by virgin male mice, modulated by OTR signaling. We further show that pup sensory information is processed in an OTR-dependent manner within the bed nucleus of the stria terminalis and the medial preoptic area. Together, these findings suggest that in virgin males, Aro+ neurons specifically respond to pup stimuli, with OTR further modulating this response to promote aggression.