Microglia motility depends on neuronal activity and promotes structural plasticity of spines in the hippocampus

Nebeling Nebeling1, Stefanie Poll1, Lena Schmid1, Manuel Mittag1, Julia Steffen1, Kevin Keppler1, Martin Fuhrmann1


Microglia, the resident immune cells of the brain, play a complex role in health and disease. They actively survey the brain parenchyma by physically interacting with other cells and structurally shaping the brain. Yet, the mechanisms underlying microglia motility and their significance for synapse stability, especially during adulthood, remain widely unresolved. Here we investigated the impact of neuronal activity on microglia motility and its implication for synapse formation and survival. We used repetitive two-photon in vivo imaging in the hippocampus of mice to simultaneously study microglia motility and their interaction with synapses. We manipulated neuronal activity using pharmacologic and chemogenetic approaches. Furthermore, we compared microglia motility in the cortex with their motility in the hippocampus under awake and anesthetized conditions. We found that microglia process motility depended on neuronal activity. Interestingly, microglia contact rates with individual dendritic spines were associated with their stability. These results suggest that microglia are not only sensing neuronal activity, but participate in synaptic rewiring of the hippocampus during adulthood, which has profound relevance for learning and memory processes.