| Project/Area Number |
09680796
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neuroscience in general
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
ITO Isao KYUSHU UNIVERSITY, FACULTY OF SCIENCE, ASSOCIATE PROFESSOR, 大学院・理学研究科, 助教授 (20183741)
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| Co-Investigator(Kenkyū-buntansha) |
伊藤 功 九州大学, 大学院・理学研究科, 助教授 (20183741)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | HIPPOCAMPUS / NMDA RECEPTOR / ィイD2εィエD2 1 SUBUNIT / ィイD2εィエD2 2 SUBUNIT / SYNAPSE / CA3 PYRAMIDAL NEURON / CA1錐体細胞 |
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| Research Abstract |
Recently, by examining the effects of targeted disruption of the GluR ィイD2εィエD2 1(NR2A)and GluR ィイD2εィエD2 2(NR2B)subunits on NMDA receptor activities, we have shown that NMDA receptors operating at different CA3 pyramidal cell synapses might have different subunit compositions. In this project, we confirmed our previous observation by pharmacological analyses using Ro 25-6981 and ifenprodil, the GluR ィイD2εィエD2 2 subunit selective NMDA receptor antagonists. Next, we examined the effects of the GluR ィイD2εィエD2 1 subunit disruption on NMDA receptor-mediated currents in response to glutamate applied iontophoretically. NMDA receptor-mediated currents of the GluR ィイD2εィエD2 1 mutant mice were reduced to one-half that of the wild-type mice both in the apical dendrite and in the basal dendrite of CA3 pyramidal neurons. We also examined the postnatal developments of the long-term potentiation(LTP)in the CA3 region. The development of LTP at the CA3 stratum radiatum synapses closely followed the development of the GluR ィイD2εィエD2 1 subunit, and the GluR ィイD2εィエD2 1 mutation strongly suppressed this LTP. The LTP at the CA3 stratum oriens synapses was not affected significantly by the mutation at all ages. Then, we examined the effects of the GluR ィイD2εィエD2 1 subunit disruption on NMDA EPSCs at two types of synapses on the basal dendrites of CA3 pyramidal neurons. The GluR ィイD2εィエD2 1 subunit disruption resulted in a significant reduction of NMDA EPSCs in the commissural/associational-CA3 synapse, whereas NMDA EPSCs in the commissural-CA3 synapse were apparently unaffected. Our data indicate that synapse-selective sorting of the GluR ィイD2εィエD2 subunits is also found in the wild-type mice and that this targeted distribution is dependent on the types of synaptic input but not on the cell polarity.
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