| Co-Investigator(Kenkyū-buntansha) |
NAGASHIMA Masabumi Hokkaido Univ., School of Medicine, Asso. Prof., 大学院・医学研究科, 助教授 (40241319)
INOUE Kaoru Hokkaido Univ., College of Medical Technology, Prof., 医療技術短期大学部, 教授 (80133718)
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| Research Abstract |
In the research project, we studied metabotropic glutamate signaling to reveal the molecular anatomy and its role in synapse development and plasticity. We analyzed the following items; 1) GTP-binding protein and phospholipases that function at Purkinje cell synpases, 2) Purkinje cell synapse formation in knockout mice lacking GTP-binding protein and phospholipase, 3) the form of persistent multiple innervation in miceiacking mGluR1 and GluRδ2, and 4) NMDA-type glutamate receptors at granule cell synapses. Distinct synapse localization of these signaling molecules were clarified. Moreover, we found distinct roles played by mGluR1 and GluRδ2 in the elimination process of surplus climbing fibers. mGluR1 signaling is essential to homotypic competition among climbing fibers for the proximal dendritic segment of Purkinje cells, whereas GluRδ2 is important in heterotypic competition between parallel fibers and climbing fibers. With both functions, Purkinje cells can establish the territorized innervation underlying LTD induction and cerebellar motor learning.
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