2010 Fiscal Year Final Research Report
GABAergic inhibition regulates developmental synapse elimination in the cerebellum
| Project/Area Number |
21700346
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neuroscience in general
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| Research Institution | The University of Tokyo |
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Principal Investigator |
NAKAYAMA Hisako The University of Tokyo, 大学院・医学系研究科, 特任研究員 (70397181)
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| Project Period (FY) |
2009 – 2010
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| Keywords | シナプス / 神経回路 / 発達 / 小脳 / プルキンエ細胞 / 登上線維 / シナプス刈り込み / GABA |
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| Research Abstract |
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, conditional deletion of GAD67 from PCs and GABAergic interneurons or pharmacological inhibition of cerebellar GAD activity. The impaired CF synapse elimination was rescued by enhancing GABAA receptor sensitivity in the cerebellum by locally applied diazepam. Our electrophysiological and Ca^<2+> imaging data suggest that GABAA receptor-mediated inhibition onto the PC soma from molecular layer interneurons influences CF-induced Ca^<2+> transients in the soma and regulates CF synapse elimination from postnatal day 10 (P10) to around P16.
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