The neural control of social behaviors in rodents requires the encoding of pheromonal cues by the vomeronasal system. Here we show that the typical preference of male mice for females is eliminated in mutants lacking oxytocin, a neuropeptide modulating social behaviors in many species. Ablation of the oxytocin receptor in aromatase-expressing neurons of the medial amygdala (MeA) fully recapitulates the elimination of female preference in males. Further, single-unit recording in the MeA uncovered significant changes in the sensory representation of conspecific cues in the absence of oxytocin signaling. Finally, acute manipulation of oxytocin signaling in adults is sufficient to alter social interaction preferences in males as well as responses of MeA neurons to chemosensory cues. These results uncover the critical role of oxytocin signaling in a molecularly defined neuronal population in order to modulate the behavioral and physiological responses of male mice to females on a moment-to-moment basis.
Oxytocin is a hormone that promotes milk production, contractions during childbirth, and many social interactions in humans and other creatures. It has also been implicated in conditions like autism or schizophrenia, which show altered social interactions. Oxytocin is made and released by cells in the brain called neurons. The oxytocin-producing neurons are clustered in a brain region called the hypothalamus, and oxytocin can act over a long distance in the brain or in the body. Many mammals detect chemical signals called pheromones that are involved in social interactions. These chemicals are detected by neurons in a structure within the cartilage of the nose called the vomeronasal organ. Pheromone-sensing neurons in the vomeronasal organ connect with another part of the brain called the medial amygdala. The medial amygdala, in turn, connects with regions of the brain that control behavior.
Mice in particular rely on pheromones for social communication. Male and female mice respond differently to pheromones. Male mice prefer to investigate female mice to other males. The neurons in medial amygdala of male mice also become more active in response to scents from females than from males. Oxytocin is known to act on the medial amygdala, but its exact role in the male’s preference for females and their scents is not known.
Now, Yao et al. show that oxytocin controls male preference for interacting with females and their scents by turning on neurons in the medial amygdala. In the experiments, male mice genetically engineered to lack oxytocin do not prefer female mice to other males, and they also appear unable to distinguish male and female scents. These mice also have less activity in the neurons of the medial amygdala when exposed to females and their scents. Directly manipulating these neurons and the oxytocin receptors on them also altered sex-preferences in male mice.
The experiments show that oxytocin alters the behaviors of male mice in response to females or their scents by manipulating a specific set of brain cells. More studies of these cells or their interactions with oxytocin might help scientists understand oxytocin-liked diseases that impair social interactions or develop new treatments for conditions like autism or schizophrenia.