Project Summary

The recent past has seen major advances in our understanding of the complexity of the macrophage
landscape of the brain. Specifically, bulk and single-cell transcriptomics and advanced cytometry have
defined distinct brain macrophage populations in the parenchyma and border locations, such as the
perivascular niches, the meninges and choroid plexus. Likewise, using the mouse as a model system we
have come to appreciate that brain macrophages activate distinct response modules when triggered in
pathology, including pro-inflammatory and dampening signatures. Interference with these modules bears
potential for future therapies. However, rationale approaches towards this goal will require a better definition
of the in vivo impact of these response modules with respect to their imbedding in the neuronal and glia
network, as well as emerging task division within the brain macrophage compartment in physiology and
pathophysiology. We recently established novel binary transgenic models based of ‘split Cre’ fragments that
allow dissecting functions of brain macrophage subpopulations. Here, we propose to use these newly
developed tools to investigate contributions of various brain macrophages to CNS physiology and
pathophysiology.