Vasopressin-to-oxytocin receptor crosstalk in the preoptic area underlying parental behaviors in male mice

The transition to parenthood brings significant changes in behavior toward offspring. For instance, in anticipation of their offspring, male mice shift from infanticidal to caregiving behaviors. While the release of oxytocin from the paraventricular hypothalamus (PVH) plays a critical role in paternal caregiving, it does not fully account for the entire behavioral shift. The specific downstream neurons and signaling mechanisms involved in this process remain obscure. Here, we demonstrate that PVH vasopressin neurons also essentially contribute to a paternal behavioral shift. This vasopressin signal is partially transmitted through oxytocin receptors (OTRs) expressed in the anterior commissure and medial nuclei of the preoptic area. These OTR-expressing neurons receive inputs from both PVH oxytocin and vasopressin neurons and are responsible for expressing paternal caregiving behaviors. Collectively, this non-canonical vasopressin-to-OTR crosstalk within specific limbic circuits acts as a pivotal regulator of paternal behavioral changes in mice. Neural mechanisms underlying shift toward caregiving behaviors in male animals are not fully understood. Here authors show that parental behaviors in male mice are facilitated by vasopressin released from the hypothalamus. Downstream, oxytocin receptors expressed in the preoptic area mediate this effect via noncanonical ligand–receptor crosstalk.