Hisako Nakayama    Department   School of Medicine, School of Medicine    Position   Associate Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Microglia permit climbing fiber elimination by promoting GABAergic inhibition in the developing cerebellum
Journal	Formal name：Nature Communications. Abbreviation：Nat Commun ISSN code：20411723
Domestic / Foregin	Foregin
Volume, Issue, Page	9(1),pp.2830
Author and coauthor	Hisako Nakayama†, Manabu Abe†, Chie Morimoto, Tadatune Iida, Shigeo Okabe, Kenji Sakimura, Kouichi Hashimoto*
Authorship	Lead author
Publication date	2018/07
Summary	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.
DOI	10.1038/s41467-018-05100-z
PMID	30026565