Early-life social enrichment induces divergent cognitive-emotional aging along with dorsal hippocampal VGluT1 and glial alterations

Early-life experiences can exert lasting impacts on brain function. While previous research has largely focused on early-life adversity, the long-term consequences of early-life enrichment on the aging brain remain poorly understood. In this study, we investigated the behavioral and molecular effects of communal nesting (CN, a model of early social enrichment, during postnatal day 2-9) in aged male mice. Behaviorally, CN-exposed mice preserved hippocampus-dependent recognition memory but exhibited elevated anxiety-like behaviors, with depression-like and social behaviors unaffected. Molecularly, CN induced region-specific adaptations in the dorsal hippocampus, characterized by elevated vesicular glutamate transporter-1 (VGluT1) immunoreactivity and reduced densities of microglia and astrocytes. No significant changes were detected in the ventral hippocampus. Together, these findings show the divergent effects of early social enrichment on cognitive and emotional aging and highlight the sensitivity of excitatory neurotransmission and neuroinflammation in the aging dorsal hippocampus to postnatal social experience.