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1998 Fiscal Year Final Research Report Summary

Roles of specific glutamate receptor subunits in the cerebellar long-term depression

Research Project

Project/Area Number 09480240
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 神経・脳内生理学
Research InstitutionKYOTO UNIVERSITY

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)

Project Period (FY) 1997 – 1998
Keywordscerebellum / synaptic plasticity / long-term depression / Purkinje cell / glutamate receptor / excitatory postsynaptic current
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.

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Kawaskaki,H.et al.: "Requirement of mitogen-activated protein kinase in cerebellar long-term depression"J.Biol.Chem. 274. 13498-13502 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Murashima,M.et al.: "Entire course and distinct phases of day-lasting depression of mEPSC amplitudes in cultured Purkinje neurons"J.Neurosci. 19. In Press (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanabe,D.et al.: "Ablation of cerebellar Golgi cells disrupts synaptic integration involving GABA inhibition and NMDA receptor activation in motor coordination"Cell. 95. 17-28 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawasaki,H.et al.: "Activation and involvement of p38 mitogen-activated protein kinase in glutamate-induced apoptosis in rat cerebellar granule cells"J.Biol.Chem. 272. 18518-18521 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawasaki,H. et al.: "Requirement of mitogen-activated protein kinase in cerebellar long-term depression."J.Biol.Chem.. 274. 13498-13502 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Murashima,M. and Hirano,T.: "entire course and distinct phases of day-lasting depression of mEPSC amplitudes in cultured Purkinje neurons."J.Neurosci.. in press. (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe,D. et al.: "Ablation of cerebellar Golgi cells disrupts synaptic integration involving GABA inhibition and NMDA receptor activation in motor coordination."Cell. 95. 17-28 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawasaki,H. et al.: "Activation and involvement of p38 mitogen-activated protein kinase in glutamate-induced apoptosis in rat cerebellar granule cells."J.Biol.Chem.. 272. 18518-18521 (1997)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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