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

Hisako Nakayama, Manabu Abe, Chie Morimoto, Tadatsune Iida, Shigeo Okabe, Kenji Sakimura and Kouichi Hashimoto ()
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Hisako Nakayama: Hiroshima University
Manabu Abe: Niigata University
Chie Morimoto: Hiroshima University
Tadatsune Iida: University of Tokyo
Shigeo Okabe: University of Tokyo
Kenji Sakimura: Niigata University
Kouichi Hashimoto: Hiroshima University

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-05100-z

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