論文

査読有り 国際誌
2018年7月19日

Microglia permit climbing fiber elimination by promoting GABAergic inhibition in the developing cerebellum.

Nature communications
  • Hisako Nakayama
  • ,
  • Manabu Abe
  • ,
  • Chie Morimoto
  • ,
  • Tadatsune Iida
  • ,
  • Shigeo Okabe
  • ,
  • Kenji Sakimura
  • ,
  • Kouichi Hashimoto

9
1
開始ページ
2830
終了ページ
2830
記述言語
英語
掲載種別
DOI
10.1038/s41467-018-05100-z

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.

リンク情報
DOI
https://doi.org/10.1038/s41467-018-05100-z
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30026565
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053401

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