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1998 Fiscal Year Final Research Report Summary

Roles of Glutamatergic Synaptic Transmission in Synapse Formation of Cerebellar Purkinje Cells, as Revealed by Morphological and Electrophysiological Analyses with Gene Knockout Mice.

Research Project

Project/Area Number 09680735
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

WATANABE Masahiko  School of Medicine, Hokkaido University Professor, 医学部, 教授 (70210945)

Project Period (FY) 1997 – 1998
KeywordsGlutamate receptor / GTP-binding protein / Phospholipase C / Cerebellum / GluRdelta2 / mGluR1 / Parallel fiber / Climbing fiber
Research Abstract

The GluRdelta2 is a Purkinje cell (PC)-speciflc ionotropic glutamate receptor subunit, and the mGluR1 is a PC-predominant metabotropic glutamate receptor. Both molecules are known to be important in the induction of long-term depression (LTD), a form of synaptic plasticity underlying the motor learning. In the present research project, I analyzed the cerebellum of knockout mice deficient in the GluRdelta2 and mGluR1, to elucidate their roles in PC synapse development. Serial electron microscopic examination revealed that PC dendritic spines free of synaptic contact emerged in the GluRdelta2-KO mouse, resulting in the reduction of parallel fiber synapses to nearly a half level. By contrast, all PC spines examined in the wild-type control were contacted with parallel fiber terminals, In the mGluR1-KO mouse, parallel fiber synapses were normally formed on distal PC dendrites. However, multiple innervation by climbing fibers, axons from brainstem inferior olivary nucleus, persisted in the mGluR1-KO mouse. These results suggest that GluRdelta2 is important in the stabilization and strengthening of synaptic connectivity between parallel fibers and PCs, whereas mGluR1 is involved in the elimination of supernumerary climbing fibers. Therefore, the two glutamate receptors play distinct, but essential roles in the PC synapse development, as they do in the induction of LTD at mature stages.

  • Research Products

    (60 results)

All Other

All Publications (60 results)

  • [Publications] Kurihara, H.,: "Impaired parallel fiber-Purkinje cell synapse stabilization during cerebellar development of mutant mice lacking the glutamate receptor δ2 subunit(GluRδ2)." J.Neurosci.17. 9613-9623 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Offermanns, S.,: "Impaired motor coordination and persistent multiple climbing fiber innervation of cerebellar Purkinje cells of mice lacking Gαq." Proc.Natl.Acad.Sci.USA. 94. 14089-14094 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shibata, T.,: "Glutamate transporter GLAST is expressed in the radial glia-astrocyte lineage of developing mouse spinal cord." J.Neurosci.17. 9212-9219 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Itoh, M.,: "Expression of a glutamate transporter subtype, EAAT4, in the developing human cerebellum." Brain Res.767. 265-271 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Maeno-Hikichi, Y.,: "Structure and functional expression of the cloned mouse neuronal high-affinity glutamate transporter." Mol.Brain Res.48. 176-180 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka, J.,: "Extra-junctional localization of glutamate transporter EAAT4 at excitatory Purkinje cell synapses." Neuroreport. 8. 2461-2464 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kohyama-Koganeya, A.,: "Molecular cloning of a diacylglycerol kinase isozyme predominantly expressed in rat retina." FEBS Lett.409. 258-264 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka, K.,: "Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1." Science. 276. 1699-1702 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakagawa, S.,: "Prominent expression of nuclear hormone receptor RORα 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
  • [Publications] Takayama, C.,: "Altered intracellular localization of glutamate receptor channel δ2 subunit in weaver and reeler Purkinje cells." Brain Res.745. 231-242 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamada K.,: "Changes in expression and distribution of the glutamate transporter EAAT4 in developing mouse Purkinje cells." Neurosci.Res. 27. 191-198 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ito, I.,: "Synapse-selective impairment of NMDA receptor functions in mice lacking NMDA receptor ε1 or ε2 subunit." J.Physiol.500. 401-408 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [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
  • [Publications] Harada, T.,: "Retinal glial cell glutamate transporter plays a crucial role in glutamate clearance." Proc.Natl.Acad.Sci.USA. 95. 4663-4666 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watase, K.,: "Motor discoordination and increased susceptibility to cerebellar injury in GLAST mutant mice." Eur.J.Neurosci.10. 976-988 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanabe, M.,: "Selective scarcity of NMDA receptor channel subunits in the stratum lucidum(mossy fiber-recipient layer)of the hippocampal CA3 subfield." Eru.J.Neurosci.10. 478-487 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kano, M.,: "Phospholipase Cβ4 is specifically involved in climbing fiber synapse elimination in the developing cerebellum." Proc.Natl.Acad.Sci.USA. 95. 15724-15729 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamada, K.,: "Glutamate transporter GLT-1 is transiently localized on growing axons of the mouse spinal cord before establishing astrocvtic expression." J.Neurosci.18. 5706-5713 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanabe, M.,: "Patterns of expression for the mRNA corresponding to the four isoforms of phospholipase Cβ in mouse brain." Eur.J.Neurosci.10. 2016-2025 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Manya, H.,: "Switching of platelet-activating factor acetylhydrolase catalytic subunits in developing rat brain." J.Biol.Chem.273. 18567-18572 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mitani, A.,: "Functional change of NMDA receptors related to enhancement of susceptibility to neurotoxicity in the developing pontine nucleus." J.Neurosci.18. 7941-7952 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mizuta, I.,: "Developmental expression of NMDA receptor subunits and the emergence of glutamate neurotoxicity in primary cultures of murine cerebral cortical neurons." Cell.Mol.Life Sci.54. 721-725 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kohmura, N.,: "Diversity revealed by a novel family of cadherins expressed in neurons at a synaptic complex." Neuron. 20. 1137-1151 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka, S.,: "Up-regulation of a new microglial gene, mrf-1, in response to programmed neuronal cell death and degeneration." J.Neurosci.18. 6358-6369 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakagawa, S.,: "Cytological compartmentalization in the staggerer cerebellum, as revealed by calbindin immunohistochemistry for Purkinje cells." J.Comp.Neurol.395. 112-120 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mori, H.,: "Role of the carboxyl-terminal region of the GluRε2 subunit in synaptic localization of the NMDA receptor channel in vivo." Neuron. 21. 571-580 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ikeda, K.,: "Distribution of prepro-nociceptin/orphanin FQ mRNA and its receptor mRNA in developing and adult mouse central nervous systems." J.Comp.Neurol.399. 139-151 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Toki, S.,: "Early establishment of lesion-insensitive mature barrelettes corresponding to upper lip vibrissae in developing mice." Neurusci.Res.印刷中. (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fukaya, M.,: "Spatiotemporal expression of mRNAs for PSD-95/SAP90 protein family in the mouse brain." Neurosci.Res.印刷中. (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shibata, T.,: "Different expressions of AMPA and NMDA receptor subunit mRNAs between visceromotor and somatomotor neurons of the rat lumbosacral spinal cord." J.Comp.Neurol.印刷中. (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kurihara, H.et al.: "Impaired parallel fiber-Purkinje cell synapse stabilization during cerebellar development of mutant mice lacking the glutamate receptor delta2 subunit (GluRdelta2)" J.Neurosci. 17. 9613-9623 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Offermanns, S., et al.: "Impaired motor coordination and persistent multiple climbing fiber innervation of cerebellar Purkinje cells of mice lacking Galphaq" Proc.Natl.Acad.Sci.USA. 94. 14089-14094 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shibata, T.et al.: "Glutamate transporter GLAST is expressed in the radial glia-astrocyte lineage of developing mouse spinal cord" J.Neurosci.17. 9212-9219 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Itoh, M.et al.: "Expression of a glutamate transporter subtype, EAAT4, in the developing human cerebellum" Brain Res.767. 265-271 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Maeno-Hikichi, Y.et al.: "Structure and functional expression of the cloned mouse neuronal high-affinity glutamate transporter" Mol.Brain Res.48. 176-180 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka, J.et al.: "Extra-junctional localization of glutamate transporter EAAT4 at excitatory Purkinje cell synapses" Neuroreport. 8. 2461-2464 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kohyama-Koganeya, A.et al.: "Molecular cloning of a diacylglycerol kinase isozyme predominantly expressed in rat retina" FEBS Lett. 409. 258-264 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka, K.et al.: "Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1" Science. 276. 1699-1702 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakagawa, S.et al.: "Prominent expression of nuclear hormone receptor RORalpha in Purkinje cells from early development" Neurosci.Res.28. 177-184 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takayama, C.et al.: "Altered intracellular localization of glutamate receptor channel delta2 subunit in weaver and reeler Purkinje cells" Brain Res. 745. 231-242 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamada K.et al.: "Changes in expression and distribution of the glutamate transporter EAAT4 in developing mouse Purkinje cells" Neurosci.Res.27. 191-198 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito, I.et al.: "Synapse-selective impairment of NMDA receptor functions in mice lacking NMDA receptor epsilon1 of epsilon2.subunit" J.Physiol.500. 401-408 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kano, M.et al.: "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
  • [Publications] Harada, T.et al.: "Retinal glial cell glutamate transporter plays a crucial role in glutamate clearance" Proc.Natl.Acad.Sci.USA. 95. 4663-4666 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watase, K.et al.: "Motor discoordination and increased susceptibility to cerebellar injury in GLAST mutant mice" Eur.J.Neurosci.10. 976-988 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe, M.et al.: "Selective scarcity of NMDA receptor channel subunits in the stratum lucidum (mossy fiber-recipient layer) of the hippocampal CA3 subfield" Eur.J.Neurosci. 10. 478-487 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kano, M.et al.: "Phospholipase Cbeta4 is specifically involved in climbing fiber synapse elimination in the developing cerebellum" Proc.Natl.Acad.Sci.USA. 95. 15724-15729 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamada, K.et al.: "Glutamate transporter GLT-1 is transiently localized on growing axons of the mouse spinal cord before establishing astrocytic expression" J.Neurosci. 18. 5706-5713 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe, M.et al.: "Patterns of expression for the mRNA corresponding to the four isoforms of phospholipase Cbeta in mouse brain" Eur.J.Neurosci. 10. 2016-2025 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Manya, H.et al.: "Switching of platelet-activating factor acetylhydrolase catalytic subunits in developing rat brain" J.Biol.Chem.273. 18567-18572 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mitani, A.et al.: "Functional change of NMDA receptors related to enhancement of susceptibility to neurotoxicity in the developing pontine nucleus." J.Neurosci.18. 7941-7952 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mizuta, I.et al.: "Developmental expression of NMDA receptor subunits and the emergence of glutamate neurotoxicity in primary cultures of murine cerebral cortical neurons" Cell.Mol.Life Sci. 54. 721-725 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kohmura, N.et al.: "Diversity revealed by a novel family of cadherins expressed in neurons at a synaptic complex" Neuron. 20. 1137-1151 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka, S.et al.: "Up-regulation of a new microglial gene, mrf-1, in response to programmed neuronal cell death and degeneration" J.Neurosci.18. 6358-6369 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakagawa, S.et al.: "Cytological compartmentalization in the staggerer cerebellum, as revealed by calbindin immunohistochemistry for Purkinje cells." J.Comp.Neurol.395. 112-120 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mori, H.et al.: "Role of the carboxyl-terminal region of the GluRepsilon2 subunit in synaptic localization of the NMDA receptor channel in vivo" Neuron. 21. 571-580 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ikeda, K.et al.: "Distribution of prepro-nociceptin/orphanin FQ mRNA and its receptor mRNA in developing and adult mouse central nervous systems" J.Comp.Neurol. 399. 139-151 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Toki, S.et al.: "Early establishment of lesion-insensitive mature barrelettes corresponding to upper lip vibrissae in developing mice." Neurusci.Res.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukaya, M.et al.: "Spatiotemporal expression of mRNAs for PSD-95/SAP90 protein family in the mouse brain" Neurosci.Res.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shibata, T.et al.: "Different expressions of AMPA and NMDA receptor subunit mRNAs between visceromotor and somatomotor neurons of the rat lumbosacral spinal cord." J.Comp.Neurol.(in press).

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

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Published: 1999-12-08  

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