Inhibition of oxytocin neurons during key periods of development has long-term behavioural and body composition effects

Oxytocin (OT) is a neuromodulator of social behaviour in mammals and accumulative data support the concept of a critical period for OT action during infancy. However, it is possible that the specific functions of OT depend on different time periods of action. In this study, we aimed to determine whether there are developmental stages during which OT-expressing neurons play a decisive role with long-term consequences. To this end, we chemogenetically inhibited OT-expressing neurons during three critical periods of development (in infants, juveniles, and young adults) in male and female mice, followed by a longitudinal study to assess behaviour and metabolic perturbations. The most pronounced behavioural effects are observed after inhibition during infancy in both sexes. Notably, social memory is consistently impaired in males, regardless of the inactivation period. From a metabolic perspective, in adulthood, an increase in body weight is observed in all cohorts of males but fat mass and adipocyte size increase after inhibition of OT-expressing neurons during juvenile period. In addition, we observed a significant delay in the day of birth and an alteration in feeding behaviour in neonates after inhibiting OT-expressing neurons around the time of birth. Thus, inhibition of OT neurons during three postnatal periods has direct, distinct, and long-lasting consequences on social behaviour and metabolism, depending on the sex and on the timing of inactivation. Our results also demonstrate a role of foetal/neonate oxytocin neurons in the timing of birth and in early feeding behaviour.