Neonatal oxytocin administration restores impaired ultrasonic vocalizations in a mouse model of 3q29 deletion syndrome

Abstract

The 3q29 microdeletion is a highly penetrant genetic risk factor for neuropsychiatric disorders, such as autism spectrum disorder (ASD) and schizophrenia. Although adult mouse models (Df/+) with this deletion exhibit robust social deficits, their early developmental trajectories are unknown. Here, we investigated neonatal communicative behaviors and the underlying oxytocin (OXT) system in Df/+ pups. On postnatal day 7, Df/+ pups emitted significantly fewer isolation-induced ultrasonic vocalizations (USVs) than did their wild-type littermates. This behavioral deficit was accompanied by a significant reduction in the number of oxytocinergic neurons within the hypothalamic paraventricular nucleus, as identified by Neurophysin 1 and OXT immunoreactivities. Notably, acute exogenous OXT restored the impaired USVs to normal levels, whereas arginine vasopressin did not. Furthermore, the baseline OXT receptor expression remained unaltered. These findings suggest that a deficiency in endogenous OXT, rather than receptor dysfunction, may drive impaired USVs in this model. As the early OXT system is essential for the maturation of social circuits, our results suggest that the neonatal period is a critical developmental window. Deficient OXT signaling during this specific stage may fundamentally alter the developmental trajectory of patients with ASD.