1997 Fiscal Year Final Research Report Summary
Regulatory mechanisms on the postsynaptic receptor sensitivity
| Project/Area Number |
07408026
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
神経・脳内生理学
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| Research Institution | University of Tokyo |
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Principal Investigator |
TAKAHASHI Tomoyuki University of Tokyo Graduate School of Medicine Professor, 大学院・医学系研究科, 教授 (40092415)
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| Co-Investigator(Kenkyū-buntansha) |
TSUJIMOTO Tetsuhiro University of Tokyo Graduate School of Medicine Research Associate, 大学院・医学系研究科, 助手 (40212055)
MANABE Toshiya University of Tokyo Graduate School of Medicine Lecturer, 大学院・医学系研究科, 講師 (70251212)
ONODERA Kayoko University of Tokyo Graduate School of Medicine Lecturer, 大学院・医学系研究科, 講師 (00053091)
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| Project Period (FY) |
1995 – 1997
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| Keywords | PKC / NMDA receptor / Pipette perfusion / Phorbol ester / Mg / Whole-cell rccording / Phosphorylation / Synaptic plasticity |
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| Research Abstract |
Synaptic plasticity is produced in part by changes in postsynaptic receptors. In this project, we attempted to elucidate a mechanism underlying changes in postsynaptic receptor sensitivity. First we found that AMPA receptor in the postsynaptic density (PSD) fraction can be phosphorylated in a Ca and calmodulin-dependent manner, supporting the hypothesis that phosphorylation of AMPA receptor is involved in the expression of long-term potentiation of synaptic efficacy in hippocampus. We next addressed a role of NMDA receptor subunits in cerebellar granule cells by applying patch clamp techniques to the mice with their NMDA receptor subunits ablated by gene targeting. We found that epsilonl subunit contributes to shortening of NMDA receptor-mediated synaptic currents, whereas epsilon3 subunit reduces the sensitivity of NMDA rcceptor to Mg block, thereby both contributing to form mature postsynaptic rcceptors. About NMDA receptors in hippocampus, we have found that epsilon2 subunit play a crucial role in the formation of long-term depression (LTD) at the Schaffer collatral-CA1 pyramidal synapses in neonatal animals. Lastly, we tested the effect of the protein kinase C (PKC) activator on EPSCs recorded from thc auditory relay neuron in the medial nucleus of trapezoid body. A phorbol ester PDBu applied into the neuron through patch pipette perfusion greatly augmented the NMDA receptor-mediated EPSCs without affecting the AMPA rcceptor-mediated ones. This effect of phorbol ester was not due to the Mg unblock. We suggest that potentiation of NMDA-EPSCs by PKC activation would contribute to the induction of LTP.
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[Publications] Yokoi M,Kobayashi K,Manabe T,Takahashi T,Sakaguchi I,Katsuura, Shigemoto R,Ohishi H,Nomura S,Nakamura K,Nakao K,Katsuki M,Nakanishi S: "Impairment of hippocampal mossy fiber LTDin mice lacking mGLUR2" Science. 273. 645-647 (1996)
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「研究成果報告書概要(欧文)」より
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