Identification of hyper‐ramified microglia in the CA1 region of the mouse hippocampus potentially associated with stress resilience

Abstract Recent studies have indicated that some individuals are less affected by stress, and such individuals are called resilient. This study aimed to determine whether the specific phenotype of microglia might be involved in resilience using the social defeat stress paradigm. Male C57BL/6J (B6) mice were attacked by aggressive male ICR mice for five consecutive days. After stress exposure, the social behaviour was reduced in about half of the B6 mice (vulnerable), whereas no such change was observed in the remaining half of the B6 mice (resilient). Anxiety‐like behaviour was increased in vulnerable mice compared with resilient mice and non‐stressed controls. However, depression‐related behaviour was comparable between the three groups. The morphological characteristics of microglia in the CA1 region of the dorsal hippocampus in non‐stressed controls and resilient mice differed from those in vulnerable mice. Interestingly, the voxel densities of GABAergic and glutamatergic synaptic puncta colocalized with microglia were higher in resilient mice than in non‐stressed controls and vulnerable mice. Microglia were then objectively classified into three morphological types by hierarchical cluster analysis. The appearance of type I microglia resembled the so‐called resting ramified microglia and represented the major population of microglia in non‐stressed controls. Type II microglia exhibited a de‐ramified morphology and accounted for 60% of the microglia in vulnerable mice. Type III microglia showed a hyper‐ramified morphology and represented more than half of the microglia in resilient mice. These results suggest that hyper‐ramified microglia in the hippocampus may be associated with stress resilience via the modulation of synaptic transmission.