ナカヤマ ヒサコ   Hisako Nakayama
  中山 寿子
   所属   医学部 医学科
   職種   助教
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 GABAergic inhibition regulates developmental synapse elimination in the cerebellum.
掲載誌名 正式名:Neuron
略  称:Neuron
ISSNコード:08966273
掲載区分国外
巻・号・頁 74(2),384-396頁
著者・共著者 NAKAYAMA Hisako†, MIYAZAKI Taisuke, KITAMURA Kazuo, HASHIMOTO Kouichi, YANAGAWA Yuchio, OBATA Kunihiko, SAKIMURA Kenji, WATANABE Masahiko, KANO Masanobu*
発行年月 2012/04
概要 Functional neural circuit formation during development involves massive elimination of redundant synapses. In the cerebellum, one-to-one connection from excitatory climbing fiber (CF) to Purkinje cell (PC) is established by elimination of early-formed surplus CFs. This process depends on glutamatergic excitatory inputs, but contribution of GABAergic transmission remains unclear. Here, we demonstrate impaired CF synapse elimination in mouse models with diminished GABAergic transmission by mutation of a single allele for the GABA synthesizing enzyme GAD67, by conditional deletion of GAD67 from PCs and GABAergic interneurons or by pharmacological inhibition of cerebellar GAD activity. The impaired CF synapse elimination was rescued by enhancing GABA(A) receptor sensitivity in the cerebellum by locally applied diazepam. Our electrophysiological and Ca2+ imaging data suggest that GABA(A) receptor-mediated inhibition onto the PC soma from molecular layer interneurons influences CF-induced Ca2+ transients in the soma and regulates CF synapse elimination from postnatal day 10 (P10) to around P16.
DOI 10.1016/j.neuron.2012.02.032.
PMID 22542190