Protocol for brain-wide or region-specific microglia depletion and repopulation in adult mice

The advent of tools enabling the direct manipulation of microglia has furthered our understanding of their role in health and disease. Here, we present a detailed protocol allowing for microglia turnover in adult CX3CR1creERT2× iDTR or CX3CR1creERT2× iDTR × tdTomatofloxmice, either in a brain-wide or region-specific manner, and their subsequent isolation for downstream applications. This protocol may be used to explore microglia biology and their putative region-specific heterogeneous functional diversity, expanding our understanding of their importance in various neuroinflammatory conditions.