ナカヤマ　ヒサコ   Hisako Nakayama   中山　寿子    所属   医学部 医学科    職種   准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Microglia permit climbing fiber elimination by promoting GABAergic inhibition in the developing cerebellum
掲載誌名	正式名：Nature Communications. 略　 称：Nat Commun ISSNコード：20411723
掲載区分	国外
巻・号・頁	9(1),pp.2830
著者・共著者	Hisako Nakayama†, Manabu Abe†, Chie Morimoto, Tadatune Iida, Shigeo Okabe, Kenji Sakimura, Kouichi Hashimoto*
担当区分	筆頭著者
発行年月	2018/07
概要	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