Region-specific neural activity changes and hierarchical instability following social isolation.

Social hierarchy contributes to maintaining group stability and coordination; yet, how social isolation affects hierarchical dynamics remains poorly understood. Although social isolation is a potent psychosocial stressor, its influence on social rank, stability, and the underlying neural mechanisms has not been clearly delineated. We established two complementary tube-test-based behavioral paradigms to investigate how isolation modulates rank status, social stability, and competitive behaviors: a rank change model assessing pre- and post-isolation rank shifts and a daily rank-trace model capturing gradual changes over time. Behavioral analyses revealed attenuated distinctions in push and retreat behaviors following isolation. c-Fos mapping demonstrated region-specific neural responses: medial prefrontal cortex activity decreased in mice that advanced in rank after long-term isolation, whereas lateral habenula activity increased in the same group following short-term isolation. Collectively, social isolation is associated with disrupted hierarchical stability and distinct, region-specific patterns of neural activity in brain areas linked to social behavior.