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ANALYSIS Of FUNCTIONAL MECHAMISM OF GLUTAMATE RECEPTORS IN NEURO-LOGICAL MUTANT MICE BY PHOTOMETRIC SYSTEM.

Research Project

Project/Area Number 07458198
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Nerve anatomy/Neuropathology
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

INOUE Yoshiro  Hokkaido Univ.Sch.of Medicine, professor, 医学部, 教授 (20051584)

Co-Investigator(Kenkyū-buntansha) ICHIKAWA Ryoichi  Hokkaido Univ.Sch.of Medicine, instructor, 医学部, 助手 (10223091)
NAGASHIMA Masabumi  Hokkaido Univ.Sch.of Medicine, lecturer, 医学部, 講師 (40241319)
TAKAYAMA Chitoshi  Hokkaido Univ.Sch.of Medicine, lecturer, 医学部, 講師 (60197217)
WATANABE Masahiko  Hokkaido Univ.Sch.of Medicine, associate professor, 医学部, 助教授 (70210945)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥5,100,000 (Direct Cost: ¥5,100,000)
KeywordsGLUTAMATE RECEPTORS / OPTICAL IMAGING / MUTANT MICE / CEREBELLUM / REELER MUTANT / KNOCK-OUT MOUSE / GABA / STAGGERER MUTANT / 神経奇形マウス / パッチクランプ法 / プルキンエ細胞 / ソーラーマウス
Research Abstract

1 The diversed oxpression of NMDA receptor subunits (epsilon1, epsilon2, epsilon3, epsilon4 and zeta1) and delta2 subunit were elucidated in the mouse cerebellum during development. In addition, expressions of NMDA receptor subunits in the adult normal mice were different from those of the reeler and straggerer mutants in combination of subunits expressed. Thus expression of NMDA receptor subunits might be influenced by the extrinsic factors like the afferent input. The delta2 subunit tended to accumulate in the dendritic spines of the Purkinje cells closely related with synaptic formation of parallel fibers.
2 The mice defective in glutamate receptor gene were generated. the epsilon1 mutant shows a moderate deficiency in spatical learning, significant reduction of the NMDA receptor channel current and LTP at the hippocumpus. The mutant mice defective in the epsilon1 subunit showed on suckling response and died shortly after birth. This disorder resulted in abnormal termination of the trigenimal afferent fibers. The epsilon4 mutant showed only a reduced spontaneous activity, bur not any morphological abnormality. By delta2 mutant this subunit is an important factor in strength and stability of synaptic connection between dendritic spines and parallel fibers.
3 The electrophysiological system for electric stimulation, electrophoretic injection and putch-clump was set up partially by this gland, and were successfully used for fine labeling of the climbing fibers from the olivary nucleus. The optical imaging system (Deltaron 1700) was also set up and the reaction of the Purkinje cells under stimulation of the parallel fibers was recorded, but the usage for analysis of the glutamate receptor functions was remained as a future problem.

Report

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

    (64 results)

All Other

All Publications (64 results)

  • [Publications] M.Watanabe: "“Selective scarcity of NMDA receptor channel subunits in the stratum lucidum (mossy fiber-recipient layer) of the hippocampal CA3 subfield."" European of Neuroscience. in press. (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Offermanns: "“Impaired motor coordination and persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking G alpah q."" Proc.Natl.Acad.Sci.USA. 94. 14089-19094 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Kurihara: "“Impaired parallel fiber-Purkinje cell synapse stabilization during cerebellar development of mutant mice lacking the glutamate receptorδ 2 subunit(GluR δ 2)."" J.Neuroscience. 17. 9613-9623 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakagawa, S.: "Prominent expression of nuclear hormone receptor ROPa in Purkinje cells from early development." Neurosci.Res. 28. 177-184 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ito, I: "Synapse-selective impairment of NMDA receptor functions in mice lacking NMDA receptor e1or e2 subunit." J.Physiol. 500. 401-408 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kano, M: "Persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking mGluR1." Neuron. 18. 71-79 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Nakagawa: "“Altered geneexpression of the N-methyl-D-aspartate receptor channel subunits in Purkinje cells of the staggerer mutant mouse."" Europian J of Neuroscience. 8. 2644-2651 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takayama C: "Altered intracellular localization of the glutamate receptor channel δ2 subunit in weaver and reeler Purkinje cells" Brain Res. 745. 2644-2651 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe M: "Modified N-methyl-D-aspartate receptor subunit expression emerges in reeler Purkinje cells after accomplishment of the adult wild-type expression." Neuroscience Res. 335-344 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 渡辺 雅彦: "中枢神経系の発達とNMDA型グルタミン酸受容体発現調節" 解剖. 16. 517-522 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kutsuwada T: "Impairment of suckling response,trigeminal neuronal pattern formation and hippocampal LTD in NMDA receptor ε 2 subunit mutant mice." Neuron. 16. 333-334 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakagawa S: "Regional variation in expressions of calbindin and inositol 1,4,5-trisphosphate receptortype 1 mRNAs in the cerebellum of the staggerermutant mouse." Europian J of Neuroscience. 8. 1401-1407 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takayama C: "Developmental changes in expression and distribution of the glutamate receptor channel δ 2 subunit according to the Purkinje cell maturation" Developmental Brain Res. 92. 147-155 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kano M: "Impaired synapses elimination during cerebellar development in PKC γ mutant mice." Cell. 83. 1223-1231 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 渡辺 雅彦: "脳の発達とグルタミン酸受容体" 化学と生物. 34. 7-9 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 渡辺 雅彦: "NMDA型グルタミン酸受容体サブユニット" 細胞. 28. 7-12 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe M: "Development dynamics of gene expression for NMDA receptor channel." The Ionotropic Glutamate receptors. 189-218 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe M: "Developmental regulation of ionotropic glutamate receptor gene expression and functionalcorrelation." Recept Dynamics in Neural Development(edited by CH Shaw). CRC press. 73-89 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ikeda K: "Reduced spontaneous activity of mice defective in the ε 4 subunit of the NMDA receptor channel." Molecular Brain Res. 33. 61-71 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe M: "Cerebellum of the adult reeler mutant mouse contains two Purkinje cell populations with respect to gene experssion for the N-methyl-D-aspartate receptor channel." Neuroscience Res. 22. 335-345 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kashiwabuchi N: "Impairment of motor coordination,Purkinje cell synaptic formation and cerebellar long-term depression in GluR δ 2 mutant mice." Cell. 81. 245-252 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takayama C: "Light-and electron-microscopic localization of the glutamate receptor channel δ 2 subunit in the mouse Purkinje cell." Neurosci Lett. 188. 89-92 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sakimura K: "Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor ε 1 subunit." Nature. 373(12). 151-155 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Watanabe, K.Sakimura, T.Manabe, K.Misima, Y.Inoue: ""Selective scarcity of NMDA receptor channel subunits in the stratum lucidum (mossy fiber-recipient layr) of the hippocampal CA3 subfield."" European J of Neuroscience. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Offermanns, K.Hashimoto, M.Watanabe, W.Sun, H.Kurihara, R.F.Thompson, Y.Inoue, M.Kano and M,I,Simon: ""Impaired motor coordination and persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking G alpha q."" Proc.Natl.Acad.Sci.USA. 94. 14089-14094 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Kurihara, K.Hashimoto, M.kano, C.Takayama, K.Sakimura, M.Mishima, Y.Inoue, M.Watanabe: ""Impaired parallel fiber-Purkinje cell synapse stabilization during cerebellar development of mutant mice lacking the glutamate receptor delta2 subunit (GluR delta2)."" J.Neuroscience. 17. 9613-9623 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakagawa, S., Watanabe, M., and Inoue, Y.: ""Prominent expression of unclear hormone receptor RORa in Purkinje cells from early development."" Neurosci.Res.28. 177-187 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ito, I., Futai, K., Katagiri, H., Watanabe, M., Sakimura, K., Mishina, M., and Sugiyama, H.: ""Synapse-selective impairment of NMDA receptor functions in mice lacking NMDA receptor el or e2 subunit."" J.Physiol. 500. 401-408 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kano, M,.Hashimoto, K., Kurihara, H., Watanabe, M., Inoue, Y., Aiba, A., and Tonegawa, S.: ""Persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking mGluR1."" Neuron. 18. 71-79 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Nakagawa, M.Watanabe, and Y.Inoue: "Altered geneexpression of the N-methyl-D-aspartate receptor channel subunits in Purkinje cells of the staggerer mutant mouse"" Europian J of Neuroscience. 8. 2644-2651 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takayama C,Nakagawa S,Watanabe M,Kurihara H,Mishina M and Inoue Y.: ""Altered intracellular localization of the glutamate receptor channel delta2 subunit in weaver and reeler Purkinje cells"" Brain Res. 745. 231-242 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe M.Noise IM and Inoue Y.: ""Modified N-methyl-D-aspartate receptor subunit expression emerges in reeler Purkinje cells after accomplishment of the adult wild-type expression."" Neuroscience Res. 335-344 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe M.: ""Dynamic Regulation of the NMDA Receptor Channel Subunits in the Central Nervous System and Their Involvement in Synaptic Plasticity and Development"" Acta Anatomica Nipponica. 71. 517-552 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kutsuwada T,Sakimura K,Manabe T.Takayama C,Katakura N,Kushiya E,Natusme R,Watanabe M,Inoue Y,Yagi T,Aizawa S,Arakawa M,Takahashi T,Nakamura Y,Mori H and Mishina M: ""Impairment of suckling response, trigeminal neuronal pattern formatio and hippocampal LTD in NMDA receptor epsilon2 subunit mutant mice."" Neuron. 16. 333-344 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakagawa S,Watanabe M and Inoue Y.: ""Regional variation in expressions of calbindin and inositol 1,4,5-trisphosphate receptor type 1 mRNAs in the cerebellum of the staggerer mutant mouse."" Europian J of Neuroscience. 8. 1401-1407 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takayama C,Nakagawa S,Watanabe M,Mishina M and Inoue Y: ""Developmental changes in expression and distribution of the glutamate receptor channel delta2 subunit according to the Purkinje cell maturation"" Developmental Brain Res. 92. 147-155 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe M.: ""Developmental regulation of ionotropic glatamate receptor gene expression and functional correlations : Receptor Dynamics in Neural Development (Ed.by ShawCA)"" CRC press, Boca Raton , New York, Tokyo. 73-89 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe M: ""Developmental dynamics of gene expression for NMDA receptor channel"" The Ionotropic Glutamate Receptors. 189-218 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kano M,Hashimoto K,Chen C,Abeliovich A,Aiba A,Kurihara H,Watanabe M,Inoue Y,and Tonegawa S: ""Impaired synapses ellimination during cerebellar development in PKC gamma mutant mice"." Cell. 83. 1223-1231 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe M.: ""Glutamate receptors and brain development"" Chemistry and biology. 34. 7-9 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe M.: ""Involvement of the NMDA receptorchannel in synaptic Plasticity and development"" Cell. 28(2). 7-12 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ikeda k, Araki K,Takayama C,Inoue Y,Yagi T,Aizawa S and Mishina M.: ""Reduced spontaneous activity of mice defective in the epsilon4 subunit of the NMDA receptor channel."" Molecular Brain Res. 33. 61-71 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe M,Nakagawa S,Takayama C,Nagashima M,Inoue K,Ichikawa R and Inoue Y.: ""Cerebellum of the adult reeler mutant mouse contains two Purkinje cell populations with respect to gene expression for the N-methyl-D-aspartate receptor channel."" Neuroscience Res. 22. 335-345 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kashiwabuchi N,Ikeda K,Araki K,Hirano T,Shibuki K,Takayama C,Inoue Y,Kutsuwada T,Yagi T,Kang Y,Aizawa S and Mishina M.: ""Impairment of motor coordination, Purkinje cell synaptic formation and cerebellar long-term depression in GluR delta2 mutant mice."" Cell. 81. 245-252 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takayama C,Nakagawa S,Watanabe M,Mishina M and Inoue Y: ""Light- and electron-microscopic localization oif the glutamate receptor channel delta2 subunit in the mouse Purkinji cell."" Neurosci Lett.188. 89-92 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sakimura K,Kutsuwada T,Ito I,Mnabe T,Takayama C,Kushiya E,Yagi T,Aizawa S,Inoue Y,Sugiyama H and Mishina M.: ""Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor epsilon1 subunit."" Nature. 373(12). 151-155 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Watanabe: ""Selective scarcity of NMDA receptor channel subunits in the stratum lucidum(mossy fiber-recipient layer)of the hippocampal CA3 subfield."" European J of Neuroscience. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] S.Offermanns: ""Impaired motor coordination and persistent multiple climbing fiber innervation of cerebellar Pukinje cells in mice lacking G α q."" Proc.Natl.Acad.Sci.USA. 94. 14089-19094 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] H.Kurihara: ""Impaired parallel fiber-Purkinje cell synapse stabilization during cerebellar development of mutant mice lacking the glutamate receptor δ2 subunit(GluR δ2)."" J.Neuroscience. 17. 9613-9623 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakagawa,S.: "Prominent expression of nuclear hormone receptor RORa in Pukinje cells from early development." Neurosci.Res. 28. 177-184 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ito,I: "Synapse-selective impairment of NMDA receptor functions in mice lacking NMDA receptor el or e2 subunit." J.Physiol. 500. 401-408 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kano,M: "Persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking mGluRl." Neuron. 18. 71-79 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takayama C, Inoue Y: "Altered intracellular localization of the glutamate receptor channel delta2 subunit in weaver and reeler Purkinje cells." Brain Res.745. 231-244 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Watanabe M, Inoue Y: "Modified N-methyl-D-aspartate receptor subunit expression emerges in reeler Purkinje cells after accomplishment of the adult wild-type espression" Neuroscience Res. 25. 325-344 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 渡邊雅彦: "中枢神経系の発達とNMDA型グルタミン酸受容体発現調節." 解剖誌. 71. 517-522 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yamada K, Watanabe M: "EAAT4 is a post-synaptic glutamate transporter at Purkinje cell synapses." Neuroreport. 7. 2013-2017 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakagawa S, Watanabe M: "Regional variation in expressions of calbindin and inositol 1, 4, 5-trisphosphate receptor type 1 mRNAs in the cerebellum of the staggerer mutant mouse" Europian J of Neuroscience. 8. 1401-1407 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takayama C, Nakagawa S,: "Developmental changes in expression and distribution of the glutamate receptor channel δ2 subunit according to the Purkinje cell maturatior" Developmental Brain Res. 92. 147-155 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ikeda K,Araki K,Takayama C,: "Reduced spontaneous activity of mice defective in the ε4 subunit of the NMPA receptor channel." Molecular Brain Res,. 33. 61-71 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Watanabe M,Nakagawa S,: "Cerebellum of the adult reeler mutant mouse contains two Purkinje cell populations with respect to gene expression for the N-methyl-D-aspartate receptor channel." Neuroscience Res,. 77. 335-345 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kashiwabuchi N,ikeda K,: "Impairment of motor coordination,Purkinje cell synaptic formation and cerebellar long-term depression in GluR δ2 mutant mice." Cell,. 81. 245-252 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takayama C,Nakagawa S,: "Light-and electron-micro scopic localization of the glutamate receptor channel δ2 subunit in the mouse Purkinje cell." Neurosci Lett,. 188. 89-92 (1995)

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

    • Related Report
      1995 Annual Research Report
  • [Publications] Kano M,Hashimoto K,Chen C,: "Impaired synapses ellimination during cerebellar development in PKC γ mutant." Cell,. 83. 1223-1231 (1996)

    • Related Report
      1995 Annual Research Report

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

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