Continued post-weaning social isolation is associated with persistent, sex-specific changes in sociability and social interaction dynamics in mice

Early social experience is critical for the maturation of social behavior, and its disruption during juvenile development may confer long-term psychiatric vulnerability. Juvenile social isolation (j-SI) after weaning is widely used as a model of early social deprivation; however, its developmental and sex-specific effects on spontaneous social interaction remain unclear. We examined the behavioral consequences of post-weaning social isolation in male and female C57BL/6J mice (Mus musculus). Mice were individually housed from postnatal day (P)21, and spontaneous social interaction was assessed longitudinally at P35, P49, and P63 during prolonged cage-based sessions using an augmented reality-based behavioral monitoring system. Locomotor activity, inter-mouse distance, mean contact duration per initiated encounter, and interaction dynamics were quantified during the light and dark phases. Juvenile social isolation was associated with greater inter-mouse distance across most developmental stages and sex-phase combinations, whereas reductions in mean contact duration per initiated encounter varied by sex, developmental stage, and light/dark phase. Locomotor activity varied by developmental stage and sex, with late-emerging increases particularly evident during the dark phase in isolated mice. In contrast, lower interaction-partner switching in isolated males was detected only at the earliest stage (P35) during the light phase. An important design feature is that isolated mice were reunited at testing with cage mates from which they had been separated for more than two weeks and were therefore effectively unfamiliar, whereas group-housed mice were tested with continuously familiar cage mates; the reported effects therefore reflect social isolation together with its intrinsic reduction in social familiarity. These findings indicate that continued post-weaning social isolation is associated with persistent, sex-specific alterations in sociability and social interaction dynamics. Our results further suggest that juvenile social experience may shape the developmental maturation and temporal organization of social interaction across adolescence and early adulthood.