Network adaptability governs resilience and susceptibility to social defeat

Stress resilience-the ability to maintain mental health after adversity-manifests in humans and rodents as efficient threat-safety discrimination and fear extinction. Although behavioral differences between resilient and susceptible individuals are well documented, the brain-wide structural signatures that distinguish resilience, susceptibility, and impaired threat learning remain poorly defined. Using a translational mouse model of chronic social defeat stress in male C57BL/6 J mice (n = 55), combined with preregistered multimodal magnetic resonance imaging with graph-theoretical analyses, we identify structural and network-level correlates of three behavioral phenotypes. Resilient animals exhibited greater microstructural complexity in prefrontal regions, and showed signatures consistent with enhanced inhibitory gating within amygdalar circuits. In contrast, susceptible animals-defined behaviorally by fear generalization and resistance to extinction-exhibited dentate gyrus alterations across all measures, suggesting diminished microstructural adaptability. A third phenotype, impaired threat learning-mice that failed to avoid individuals from a threatening strain-was associated with altered CA1/CA2 microstructure and reduced structural connectivity in pons, pointing to disrupted hippocampal-brainstem interactions during memory consolidation. These findings demonstrate that resilience, susceptibility, and impaired threat learning arise from dissociable patterns of brain organization, with resilience reflecting adaptive circuit-level organization and susceptibility and impaired threat learning exhibiting distinct forms of microstructural and network reorganization.