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 CX₃CR₁^creERT2 × iDTR or CX₃CR₁^creERT2 × iDTR × tdTomato^flox mice, 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. For complete details on the use and execution of this protocol, please refer to Willis et al. (2020).