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

Nature Communications
Hisako NakayamaKouichi Hashimoto

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.

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Citations

Jun 5, 2019·Current Neuropharmacology·Pablo L CardozoFabíola M Ribeiro
Aug 23, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Polina A Egorova, Ilya B Bezprozvanny
Sep 18, 2020·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Hikaru ItoHidenori Aizawa
Jul 28, 2019·The Journal of Experimental Medicine·Veronika KanaMiriam Merad
Oct 28, 2019·Cells·Marcus Augusto-OliveiraMaria Elena Crespo-Lopez
Jan 25, 2020·Neurochemical Research·Miren RevueltaThomas Schmitz
Aug 3, 2019·F1000Research·Masanobu Kano, Takaki Watanabe
Jun 16, 2019·Seminars in Cell & Developmental Biology·Maude BordeleauMarie-Ève Tremblay
Jan 21, 2019·Journal of Molecular Biology·Austin FerroMarija Cvetanovic
May 3, 2021·Trends in Neurosciences·Mark B Stoessel, Ania K Majewska
Aug 1, 2021·Nature Communications·Hanxiao LiuQiaojie Xiong
Aug 21, 2021·Cellular & Molecular Immunology·Joshua D CrapserKim N Green

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