The role of microtubule cytoskeleton modulation in microglia and its effect on cognition

Microglia are resident macrophages of the central nervous system (CNS), where they act as first immune response to pathogens. Moreover, microglia are highly motile cells that are associated with regulation of CNS homeostasis and neuronal function. However, how microglia influence neurons and vice versa is poorly understood. This project investigates how microglial fine process motility and migration depends on microtubule dynamics, impinging on neuronal function and cognition. We address this research question by using mice with a microglia-specific and inducible knockout of tubulin tyrosine ligase (TTL), which is necessary for microtubule dynamics. In these mice, we carry out in vivo two-photon microscopy to characterize the role of TTL in microglia motility and migration. Moreover, we investigate neurons and microglia in the hippocampus of awake head-fixed and freely moving mice during behavior to decipher the role of microtubule dynamics in microglia and its importance for neuronal networks. To address how TTL-deficient microglia affect synapse remodeling, we investigate dendritic spines and adjacent microglia in the hippocampus during memory-related behavior. This project provides novel insights on the role of microtubules in microglia, and how this function influences learning and memory.