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Regulatory mechanisms on the postsynaptic receptor sensitivity

Research Project

Project/Area Number 07408026
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field 神経・脳内生理学
Research InstitutionUniversity of Tokyo

Principal Investigator

TAKAHASHI Tomoyuki  University of Tokyo Graduate School of Medicine Professor, 大学院・医学系研究科, 教授 (40092415)

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)
林 康紀  東京大学, 医学部(医), 日本学術振興会特別研
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥30,800,000 (Direct Cost: ¥30,800,000)
Fiscal Year 1997: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1996: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1995: ¥23,700,000 (Direct Cost: ¥23,700,000)
KeywordsPKC / NMDA receptor / Pipette perfusion / Phorbol ester / Mg / Whole-cell rccording / Phosphorylation / Synaptic plasticity / ピペット内灌流 / グルタミン酸受容体 / mGluR / セロトニン / スライス / パッチクランプ / 遺伝子ノックアウト / 長期抑圧 / 長期増強 / カルモジュリン / 興奮性シナプス応答 / タンパクリン酸化
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.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Hori Y: "Long-lasting synaptic facilitation induced by serotonin in superficial dorsal horn neurones of rat spinal cord." Journal of Physiology(London). 492. 867-876 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Silver RA: "Non-NMDA glutamate receptor occupancy and open probability at a rat cerebellar synapse with single and multiple release sites." Journal of Physiology(London). 494. 231-250 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takahashi T: "Presynaptic calcium current moduration by a metabotropic glutamate receptor." Science. 274. 594-597 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kobayashi K: "Presynaptic long-term depressionat the hippocampal mossy fiber-CA3 synapse." Science. 273. 648-650 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yokoi M: "Impairment of hippocampal mossy fiber LTD in mice lacking mGLUR2" Science. 273. 645-647 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hayashi Y: "Calcium-and calmodulin-dependentphosphorylation of AMPAtype glutamate recepter subunits by endogenous protein kinases in the post-synaptic density" MOLECULRA BRAIN RESEARCH. 46. 338-342 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hori Y,Endo K & Takahashi T: "Long-lasting synaptic facilitation induced by serotonin in superficial dorsal horn neurones of rat spinal cord." Journal of Physiology (London). 492. 867-876 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Silver RLAMBDA, Cull-Candy SG & Takahashi T: "Non-NMDA glutamate receptor occupancy and open probability at a rat cerebellar synapse with single and multiple release sites." Journal of Physiology (London). 494. 231-250 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takahashi T,Forsythe I,Tsujimoto T,Barnes-Davies M,Onodera K: "Presynaptic calcium current moduration by a metabotropic glutamate receptor" Science. 274. 594-597 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kobayashi K,Manabe T,Takahashi T: "Presynaptic long-term depresssion at the hippocampal mossy fiber-CLAMBDA3 synapse" Science. 273. 648-650 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hayashi Y,Ishida A,Katagiri H,Mishina M,Fujisawa H,Manabe T,& Takahashi T: "Calcium-and calmodulin-dependent phosphorylation of AMPA type glutamate receptoer subunits by endogenous protein kinases in the postsynaptic density." Molecular Brain Reserach. 46. 338-342 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hayashi Y: "Calcium-and calmodulin-dependent phosphorylation of AMPAtype glutamate recepter subunits by endogenous protein kinases in the post-synaptic density" MOLECULRA BRAIN RESEARCH. 46. 338-342 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takahashi T: "G Protein-Coupled Modulation of Presynaptic Calcium Currents and Transmitter Release by a GABA_B Receptor" Journal of Neuroscience. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ian D.Forsythe: "Inactivation of Presynaptic Calcium Current Contributes to Synaptic Depression at a Fast Central seSynap" Neuron. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kutsuwada T: "Impairment of suckling response,trigeminal neuronal pattern formation and hippocampal LTD in NMDA receptor ε2 subunit mutant mice" Neuron. 16. 333-344 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hori Y: "Long-lasting synaptic facilitation induced by serotonin in superficial dorsal horn neurones of rat spinal cord" Journal of Physiology(London). 492. 867-876 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Silver RA: "Non-NMDA glutamate receptor occupancy and open probability at a rat cerebellar synapse with single and multiple release sites" Journal of Physiology(London). 494. 231-250 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takahashi T: "Presynaptic calcium current moduration by a metabotropic glutamate receptor" Science. 274. 594-597 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kobayshi K: "Presynaptic long-term depression at the hippocampal mossy fiber-CA3 synapse" Science. 273. 648-650 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yokoi M: "Impairment of hippocampal mossy fiber LTD in mice lacking mGLUR2" Science. 273. 645-647 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Silver RA: "Non-NMDA receptor occupancy during transmission at rat cerebellar mossy fibre-granule cell synapses with only one functional release site." Journal of Physiology(London). 489. 16 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Larkman PM: "Adenosine 3′:5′-cyclic monophosphate mediates a 5-HT-induced response in neonatal rat motoneurons." Pflugers Arch. 430. 763-769 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takei Y: "Synapsin I deficiency results in the structural change in the presynaptic terminals in the murine nervous system." Journal of Cell Biology. 131. 1789-1800 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kutsuwada T: "Impairment of suckling response,trigeminal neuronal pattern formation and hippocampal LTD in NMDA receptor ε2 subunit mutant mice." Neuron. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hori Y: "Long-lasting synaptic facilitation induced by serotonin in superficial dorsal horn neurones of rat spinal cord." Journal of Physiology(London). (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Silver RA: "Non-NMDA glutamate receptor occupancy and open probability at a rat cerebellar synapse with single and multiple release sites." Journal of Physiology(London). (in press). (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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