Physiological and injury-induced microglial dynamics across the lifespan

Microglia are the brain's resident immune cells known for their dynamic responses to tissue and vascular injury. However, few studies have explored how microglial activity differs across the life stages of early development, adulthood, and aging. Using two-photon live imaging, we confirm that microglia in the adult cerebral cortex exhibit highly ramified processes and relatively immobile somata under basal conditions. Their responses to focal laser-induced injury occur over minutes and are highly coordinated among neighboring microglia. In contrast, neonatal microglia are denser and more mobile but less morphologically complex. Their responses to focal laser-induced injuries of capillaries or parenchymal tissue are uncoordinated, delayed, and persist over days. In the aged brain, microglia somata remain immobile under basal conditions, but their processes become less ramified. Their responses to focal injuries are coordinated but slower and less sensitive. These studies reveal the marked shifts in microglial morphology, distribution, dynamics, and injury response across the lifespan.