Roles of specific glutamate receptor subunits in the cerebellar long-term depression
| Project/Area Number |
09480240
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | KYOTO UNIVERSITY |
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Principal Investigator |
HIRANO Tomoo Graduate School of Science, Department of Biophysics, Kyoto University, Professor, 大学院・理学研究科, 教授 (50181178)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 1998: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥11,300,000 (Direct Cost: ¥11,300,000)
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| Keywords | cerebellum / synaptic plasticity / long-term depression / Purkinje cell / glutamate receptor / excitatory postsynaptic current / 興奮性シナプス電流 |
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| Research Abstract |
The cerebellar long-term depression (LTD) has been a candidate mechanism for motor learning. It is the long-lasting reduction of transmission efficacy at the granule neuron-Purkinje neuron (G-P) synapses induced by repeated conjunctive activation of an inferior olivary neuron and granule neurons. We have been analyzing cellular and molecular induction mechanism of the LTD in dissociated cell culture preparation, and have demonstrated the involvement of mGluR1 subtype of metabotropic glutamate receptors, δ2 subunit of ionotropic glutamate receptors and IP3 in the LTD induction have been reported. We examined whether MAP kinase is involved or not, and have found that PD98059, an inhibitor of MAP kinase cascade, inhibits the LTD induction, and that the conditioning stimulation inducing LTD activates MAP kinase. PD98059 suppressed the inward current induced by application of a mGluR1 agonist to a Purkinje cell, which suggests that MAP kinase activity supports the mGluR1 cascade. We also succeeded to monitor synaptic efficacy for a week after the LTD induction by measuring the miniature EPSCs amplitude before and after the LTD induction in the culture. By this method, we demonstrated that the synaptic efficacy recovers in two days after the LTD induction and that the LTD is consist of early and late phases whose induction mechanisms are distinct. The late phase required the prolonged conditioning stimulation for the induction and was dependent on both mRNA and protein syntheses. The study to clarify roles of δ2 subunit in the LTD induction is on going, using cultured Purkinje neurons prepared form δ2 knockout mice and the adeno-virus vector to express mutant δ2 proteins.
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Report
(3 results)
Research Products
(12 results)
