RESEARCH ARTICLE The role of P2Y12 in the kinetics of microglial self-renewal and maturation in the adult visual cortex in vivo Monique S Mendes1, Linh Le1, Jason Atlas1, Zachary Brehm2, Antonio Ladron-de-Guevara1,3, Evelyn Matei1, Cassandra Lamantia1, Matthew N McCall2, Ania K Majewska1,4* 1Department of Neuroscience, University of Rochester Medical Center, Rochester, United States; 2Department of Biostatistics, University of Rochester Medical Center, Rochester, United States; 3Department of Biomedical Engineering, University of Rochester, Rochester, United States; 4Center for Visual Science, University of Rochester, Rochester, United States Abstract Microglia are the brain’s resident immune cells with a tremendous capacity to autonomously self-renew. Because microglial self-renewal has largely been studied using static tools, its mechanisms and kinetics are not well understood. Using chronic in vivo two-photon imaging in awake mice, we confirm that cortical microglia show limited turnover and migration under basal conditions. Following depletion, however, microglial repopulation is remarkably rapid and is sustained by the dynamic division of remaining microglia, in a manner that is largely independent of signaling through the P2Y12 receptor. Mathematical modeling of microglial division demonstrates that the observed division rates can account for the rapid repopulation observed in vivo. Additionally, newly born microglia resemble mature microglia within days of repopulation, although morphological maturation is different in newly born microglia in P2Y12 knock out mice. Our work suggests that microglia rapidly locally and that newly born microglia do not recapitulate *For correspondence:
[email protected]. the slow maturation seen in development but instead take on mature roles in the CNS. edu Competing interests: The authors declare that no Introduction competing interests exist.