Multisensory Logic of Infant-Directed Aggression by Males.

Newborn mice emit signals that promote parenting from mothers and fathers but trigger aggressive responses from virgin males. Although pup-directed attacks by males require vomeronasal function， the specific infant cues that elicit this behavior are unknown. We developed a behavioral paradigm based on reconstituted pup cues and showed that discrete infant morphological features combined with salivary chemosignals elicit robust male aggression. Seven vomeronasal receptors were identified based on infant-mediated activity， and the involvement of two receptors， Vmn2r65 and Vmn2r88， in infant-directed aggression was demonstrated by genetic deletion. Using the activation of these receptors as readouts for biochemical fractionation， we isolated two pheromonal compounds， the submandibular gland protein C and hemoglobins. Unexpectedly， none of the identified vomeronasal receptors and associated cues were specific to pups. Thus， infant-mediated aggression by virgin males relies on the recognition of pup's physical traits in addition to parental and infant chemical cues.