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Molecular mechanism of synaptic plasticity

Research Project

Project/Area Number 07278101
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionThe University of Tokyo

Principal Investigator

SHIMIZU Takao  UNIVERSITY OF TOKYO, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院・医学系研究科, 教授 (80127092)

Co-Investigator(Kenkyū-buntansha) KASAI Haruo  PROFESSOR, NATIONAL INSTITUTE OF PHYSIOLOGICAL SCIENCES, 細胞器官研究系, 教授 (60224375)
NODA Makoto  KYOTO UNIVERSITY GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院・医学系研究科, 教授 (30146708)
MISHINA Masayoshi  The UNIVERSITY OF TOKYO, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院・医学系研究科, 教授 (80144351)
MIKI Naomasa  OSAKA UNIVERSITY, GADAUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院・医学系研究科, 教授 (40094445)
KUBOTA Kisou  NIPPON UNIVERSITY OF SOCIAL WEALFARE, PROFESSOR, 情報社会学部, 教授 (30027479)
Project Period (FY) 1995 – 1998
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥113,900,000 (Direct Cost: ¥113,900,000)
Fiscal Year 1999: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥25,000,000 (Direct Cost: ¥25,000,000)
Fiscal Year 1997: ¥26,700,000 (Direct Cost: ¥26,700,000)
Fiscal Year 1996: ¥29,500,000 (Direct Cost: ¥29,500,000)
Fiscal Year 1995: ¥29,700,000 (Direct Cost: ¥29,700,000)
KeywordsSynaptic plasticity / Knockout mice / NMDA receptor / lipid mediators / 記憶 / 公開シンポジウム / 班会議 / 若手研究者 / グルタイン酸受容体 / Gタンパク質 / 受容体 / シグナル伝達 / リン酸化酵素 / 標的遺伝子組み換え
Research Abstract

Synaptic plasticity is considered to be a fundamental mechanism of memory and learning. In this project, more than 140 scientists with different disciplines have worked to elucidate the underlying molecular mechanisms of neuronal plasticity and its biological significance. Many important molecules (glutamate receptor channels, protein kinases, receptors for lipid mediators, small GTP binding proteins etc) were cloned by these members, and their genetically deficient mice were established. By backcrossing, most mice are now congenic for more strict analyses. Using these mice, we found that NMDA receptors and protein kinases C are important for synaptic plasticity as well as synaptic maturation. Lipid mediators (prostaglandin, leukotrienes, PAF), small G-proteins are also involved in plasticity and neuronal cell migration. Using subtraction technology and others, we found various LTP or LTD-induced genes, and ther functions are currently under investigations.

Report

(6 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (40 results)

All Other

All Publications (40 results)

  • [Publications] Sakimura K. et al.: "Reduced hippocampal LTP and apatial learning in mice lacking NMDA receptor e1 subunit"Nature. 373. 151-155 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kashiwabuchi, N. et al.: "Impairment of motor coordination, Purkinje cell synapse formation and cerebellar long-term potentiation in GLURd2 mutant mice"Cell. 81. 245-252 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mori, M. et al.: "Predominant expression of platelet-activating factor receptor in the rat microglia"Journal of Neuroscience. 16. 3590-3600 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yokomizo, T. et al.: "A G-protein-coupled receptor for leukotriene B4 that mediates chemotaxis"Nature. 387. 620-624 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ushikubi, F. et al.: "Impaired febrile response in mice lacking the prostaglandin E receptor subtype EP3"Nature. 395. 281-284 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okuda-Ashitaka: "E. Nocistatin : a peptide blocking nociceptin action in pain transmission"Nature. 392. 286-289 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kobayashi, K. et al.: "Platelet-activating factor is not required for long-term potentiation in the hippocampal CA1 region"Eur. J. Neurosci.. 11. 1313-1316 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sakimura K. et al.: "Reduced hippocamal LTP and spatial learning in mice lacking NMDA receptor e1 subunit"Nature. 373. 151-155 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kashiwabuchi, N. et al.: "Impairement of motor coordination, Purkinje cell synapse formation anc cerebellar long-term potentiation in GLURd2 mutant mice"Cell 81. 245-252 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mori, M. et al.: "Predominant expression of platelet-activating factor receptor in the rat microglia"Journal of Neuroscience. 16. 3590-3600 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yokomizo, T. et al.: "A G-protein-coupled receptor for leukotniene B4 that mediates chemotaxis"Nature. 387. 620-624 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ushikubi, F. et al.: "Impaired febrile response in mice lacking the prostaglandin E receptor subtype EP3"Nature. 395. 281-284 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okuda-Ashitaka, E.: "Nocistatin : a peptide blocking nociceptin action in pain transmission"Nature. 392. 286-289 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kobayashi, K. et al.: "Platelet-activating factor is not required for long-term potentiation in the hippocampal CA1 region"Eur. J. Neurosci.. 11. 1313-1316 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kasai, H.: "Comparative Biology of Ca-dependent-exocytosisin-phdrations of kinetic diversity for secretory function"Trends Neurosci.. 22. 88-93 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hayashi, T. et al.: "The AMPA receptor interacts with and signal through the protein kinase Lyn"Nature. 397. 72-76 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kasai, H. et al.: "Multiple and diverse forms of regulated exocytosis revealed in wild tyno acid defective PC19 cells"Proc. Natl. Acad. Sai. U.S.A.. 96. 945-999 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ishii,S et al: "Impaired anaphylactic responses with intact sensitivity to endotoxin in mice lacking a PAF reccptor" J.Exp.Med. 187. 1779-1788 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kasai,H.: "Comparative Biology of Ca-dependent exocytos is:in-phibitions of Kinetic diversity for secretory function" Trends Neurosci,. 22. 88-93 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mori,H.et al: "Role of the carboxyl-terminal region of the GluRε2 subunit in synaptic localization of the NMDA receptor channel" Neuron. 21. 571-580 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hayashi,T.et al: "The AMPA receptor interacts with and signal through the protein Kinase Lyn." Nature. 397. 72-76 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kasai,H.et al: "Multiple and diverse forms of regulated exouptos is revealed in coild type and defective PC12 cells" Proc.Natl.Acad.Soi.USA. 96. 945-999 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kojima,M.et al: "Expression of Nedd2/ICH-1(caspase-2)in the developing rat retina" Neurosci.Res. 31. 211-217 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yokomizo et al.: "A G-protein-coupled receptor for leukotriene that mediates chemotaxis." Nature. 390. 7503-7522 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Uozumi,N.et al.: "A major role for cytosolic phospholipase A2 in allergic response and parturition." Nature. 390. 618-622 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Taniguchi,M.: "Efficient production of CRe-mediated site-directed recombinants through the utilization of Pur genes." Nucleic Acid. 26. 679-680 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Taniguchi,M.et al.: "Disruption of semaphorin III/D gene causes severe abnormality in peripheral nerve projection." Neuron. 19. 995-1005 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kumar,S et al.: "Origin,expressionand possible function of the two alternative spliced forms of the mouse Nedd2 mRNA" Cell Death Differentiation. 4. 379-387 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ito,K.et al.: "Kinetic diversity in the fusion of exocytotic vesicles." EMBO Journal. 16. 929-934 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mori,M.et al.: "Predominant expression of platelet-activating factor receptor in the rat brain microglia." J.Neurosci.16. 3590-3600 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ishii,S.et al.: "Bronchial hyperreacitivity,increased endotoxin lethality,and melanocytic tumorigenesis in transgenic mice overexpressing platelet-activating factor receptor." EMBOJ.16. 133-142 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kutsuwada,T.et al.: "Impaiment of suckling response,trigeminal neuronal pattern formation and hippocampal LTD in NMDA receptor e2 subunit mutant mice." Neuron. 16. 333-344 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kataoka,K.,et al.: "Transactivation activity of Maf nuclear oncoprotein is modulated by Jun,Fos,and small Maf proteins." Onogene. 12. 53-62 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kinoshita,M.,et al.: "Up-regulation of Nedd2,an ICE/Ced-3-like cystein protease,precedes ischemia-induced neuronal death in gerbil brain." J.Cerebr.Blood.F1.Met.in press. (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kasai,H.et al.: "Two components of exocytosis and endocytos is in phaeochromocytoma cells sutudied using caged-Ca2+compounds." J.Physiology. 494. 53-65 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sakimura, K. et al: "Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor ε1 subunit" Nature. 373. 151-155 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kashiwabuchi, N.: "Impairment of motor coordination, Purkinje cell synapse formation, and cerebellar LTD in Glu RS2 mutant mice" Cell. 81. 245-252 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Taira, E. et al.: "Expression and functional analysis of a novel isoform of gicerin, an isoform of cell adhesion molecule" J. Biol. Chem. 270. 28681-28687 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nakamura, M. et al.: "Identification of two isoforms of mouse neuropeptide Y-Y1 receptor qenerated by alternative splicing" J. Biol. Chem. 270. 30102-30110 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Mutoh, H. et al.: "Tissue-specific response of the human platelet-activating factor receptor gene and thyroid hormone by alternative" Proc. Natl. Acad. Sci, U. S. A.93. 774-779 (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2019-02-15  

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