Nakayama H1,2, Abe M3,4, Morimoto C1,5, Iida T6, Okabe S6, Sakimura K3,4, Hashimoto K1.
1Department of Neurophysiology, Graduate School of Biomedical and Health Sciences, Hiroshima University
2Department of Physiology, School of Medicine, Tokyo Women's Medical University
3Department of Cellular Neurobiology, Brain Research Institute
4Department of Animal Model Development, Brain Research Institute
5Department of Psychosocial Rehabilitation Graduate School of Biomedical & Health Sciences, Hiroshima University
6Department of Cellular Neurobiology, Graduate School of Medicine, University of Tokyo
Circuit refinement during postnatal development is finely regulated by neuron-neuron interactions. Recent studies suggest participation of microglia in this process but it is unclear how microglia cooperatively act with neuronal mechanisms. To examine roles of microglia, we ablate microglia by microglia-selective deletion of colony-stimulating factor 1 receptor (Csf1r) by crossing floxed-Csf1r and Iba1-iCre mice (Csf1r-cKO). In Csf1r-cKO mice, refinement of climbing fiber (CF) to Purkinje cell (PC) innervation after postnatal day 10 (P10)-P12 is severely impaired. However, there is no clear morphological evidence suggesting massive engulfment of CFs by microglia. In Csf1r-cKO mice, inhibitory synaptic transmission is impaired and CF elimination is restored by diazepam, which suggests that impairment of CF elimination is caused by a defect of GABAergic inhibition on PCs, a prerequisite for CF elimination. These results indicate that microglia primarily promote GABAergic inhibition and secondarily facilitate the mechanism for CF elimination inherent in PCs.