Post-Weaning Isolation Leaves Lasting, Sex-Specific Marks on Mouse Social Behavior

Mice separated from cage mates right after weaning show persistent, sex-specific changes in how they interact with others, according to a longitudinal behavioral study of juvenile social isolation in C57BL/6J mice.

Researchers individually housed mice from postnatal day 21 and then tracked spontaneous social interaction at postnatal days 35, 49, and 63. Using an augmented reality-based behavioral monitoring system, they quantified locomotor activity, inter-mouse distance, mean contact duration per initiated encounter, and interaction dynamics during extended cage-based sessions in both light and dark phases.

Across most developmental stages and sex-phase combinations, isolated mice kept a greater inter-mouse distance than their group-housed counterparts, suggesting a robust and lasting reduction in proximity-seeking after early social deprivation.

By contrast, reductions in mean contact duration per initiated encounter were not uniform. They varied by sex, developmental stage, and whether behavior was observed during the light or dark phase, indicating that the effects of isolation on the quality of individual social encounters are more context-dependent than the effects on distance.

Locomotor activity also differed by developmental stage and sex, with late-emerging increases particularly evident during the dark phase in isolated mice. Meanwhile, lower interaction-partner switching appeared only in isolated males, only at the earliest stage tested, day 35, and only during the light phase, a narrow and transient effect rather than a general feature of isolation.

The authors highlight an important design consideration: 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 thus reflect social isolation together with its intrinsic reduction in social familiarity, not isolation alone.

Because the study is observational in design, the findings describe associations between post-weaning isolation and later social behavior rather than demonstrating causal mechanisms. The work also cannot disentangle how much of the effect stems from the absence of social contact versus the loss of familiarity with specific partners.

Nevertheless, the results indicate that continued post-weaning social isolation is associated with persistent, sex-specific alterations in sociability and social interaction dynamics in mice. The pattern of changes suggests that juvenile social experience may shape the developmental maturation and temporal organization of social interaction across adolescence and early adulthood.

As juvenile social isolation is widely used as a model of early social deprivation, these longitudinal, sex-stratified measurements may help clarify how disrupted early social experience contributes to long-term psychiatric vulnerability, and why such vulnerability often differs between males and females.

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

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

Article References: Yamamuro, K., Takahashi, M., Okuda, M., Okumura, K., Kashida, N., Yoshihara, T., Takeda, T., Toritsuka, M., Yamauchi, T., & Makinodan, M. (2026). Continued post-weaning social isolation is associated with persistent, sex-specific changes in sociability and social interaction dynamics in mice. PLOS One, 21(10), e0361386. https://doi.org/10.1371/journal.pone.0361386

Image Credits: AI Generated

DOI: 10.1371/journal.pone.0361386

Keywords: Continued, post-weaning, social, isolation, associated, persistent, sex-specific, changes, sociability, interaction, dynamics, mice