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Molecular basis of motor learning dependent on the cerebellum

Research Project

Project/Area Number 12210011
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKyoto University

Principal Investigator

HIRANO Tomoo  Kyoto University, Graduate School of Science, Professor, 大学院理学研究科, 教授 (50181178)

Project Period (FY) 2000 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥92,400,000 (Direct Cost: ¥92,400,000)
Fiscal Year 2004: ¥22,400,000 (Direct Cost: ¥22,400,000)
Fiscal Year 2003: ¥22,400,000 (Direct Cost: ¥22,400,000)
Fiscal Year 2002: ¥22,400,000 (Direct Cost: ¥22,400,000)
Fiscal Year 2001: ¥25,200,000 (Direct Cost: ¥25,200,000)
KeywordsMotor learning / Cerebellum / Synapse / Plasticity / Glutamate / GABA / Purkinje cell / Mutant mouse / グルタミン酸受容体 / 眼球運動 / 運動失調 / シスプス可塑性 / シプナス可塑性 / リン酸化 / 脱リン酸化 / シナプス可塑性 / 培養
Research Abstract

Synaptic plasticity is the long-lasting alteration of transmission efficacy at a synapse, and has been a candidate cellular mechanism for learning and memory. Purkinje cells, sole neurons sending outputs from the cerebellar cortex, show several types of synaptic plasticity. One is the long term depression at excitatory synapses and another is the rebound potentiation at inhibitory synapses, which have been regarded as basic mechanisms for motor learning. In this study, we have been trying to elucidate the molecular mechanisms of induction, maintenance and regulation of the synaptic plasticity, and also to clarify its roles in regulation of information processing in the cerebellum and in the control of animal behavior. At inhibitory synapses we discovered the novel regulation mechanism of synaptic plasticity: the synaptic activity suppresses the induction of rebound potentiation. We also clarified molecular mechanism of that regulation. At excitatory synapses we found that calcineurin, calcium-dependent phosphatase, is implicated in the induction of late phase of long term depression. Further, we have also studied the behavior of mutant mice deficient in the ionotropic glutamate receptor δ 2 subunit, which is selectively expressed at excitatory synapses on a Purkinje cell and is necessary for the induction of long term depression. We showed that the mutant mice failed to perform adaptive modifications of reflex eye movements, which are models of motor learning. We also showed that the motor control ability of the mutant mouse was impaired more severely than that of lurcher mutant mouse, which lose all Purkinje cells during development. We analyzed the cause of sever motor discoordination and demonstrated that the δ2 subunit deficiency produces the oscillating activity in Purkinje cells by enhancing climbing fiber inputs, causing surplus movement and affecting motor control worse than no signal at all.

Report

(6 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (56 results)

All 2006 2005 2004 2003 2002 2001 2000 Other

All Journal Article (38 results) Book (1 results) Publications (17 results)

  • [Journal Article] Cerebellar regulation mechanisms learned from studies on GluR ?2, a unique glutamate-receptor-related molecule specifically expressed at parallel fiber-Purkinje cell synapses.2006

    • Author(s)
      Hirano, T.
    • Journal Title

      Mol. Neurobiol. 33

      Pages: 1-16

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Defective control and adaptation of reflex eye movements in mutant mice deficient in either the glutamate receptor ?2 subunit or Purkinje cells.2005

    • Author(s)
      Katoh, A et al.
    • Journal Title

      Eur. J. Neurosci. 21

      Pages: 1315-1326

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] DNER acts as a neuron-specific Notch ligand during Bergmann glial development.2005

    • Author(s)
      Eiraku, M et al.
    • Journal Title

      Nature Neurosci. 8

      Pages: 873-880

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Defective control and adaptation of reflex eye movements in mutant mice deficient in either the glutamate receptor δ2 subunit or Purkinje cells.2005

    • Author(s)
      Katoh, A et al.
    • Journal Title

      Eur. J. Neurosci. 21

      Pages: 1315-1326

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] DNER acts as a neuron-specific Notch ligand during Bergmann glial development.2005

    • Author(s)
      Eiraku, M et al.
    • Journal Title

      Nature Neurosci. (In Press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cerebellar regulation mechanisms learned from studies on GluR62, a unique glutamate-receptor-related molecule specifically expressed at parallel fiber-Purkinje cell. synapses.2005

    • Author(s)
      Hirano, T.
    • Journal Title

      Mol. Neurobiol. (In Press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Defective control and adaptation of reflex eye movements in mutant mice deficient in either the glutamate receptor δ2 subunit or Purkinje cells.2005

    • Author(s)
      Katoh A et al.
    • Journal Title

      Eur.J.Neurosci. (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Dual phases of migration of cerebellar granule cells guided by axonal and dendritic leading processes.2004

    • Author(s)
      Kawaji, K et al.
    • Journal Title

      Mol. Cell. Neurosci. 25

      Pages: 228-240

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Oscillating Purkinje neuron activity causing involuntary eye movement in a mutant mouse deficient in the glutamate receptor?2 subunit.2004

    • Author(s)
      Yoshida, T et al.
    • Journal Title

      J. Neurosci. 24

      Pages: 2440-2448

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Regulation of dendritic maintenance and growth by a mammalian 7-pass transmembrane cadherin.2004

    • Author(s)
      Shima, Y et al.
    • Journal Title

      Dev. Cell 7

      Pages: 205-216

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Enhanced inhibitory synaptic transmission in the cerebellar molecular layer of the GluR?2 knockout mouse.2004

    • Author(s)
      Ohtsuki, G et al.
    • Journal Title

      J. Neurosci. 24

      Pages: 10900-10907

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Dual phases of migration of cerebellar granule cells guided by axonal and dendritic leading processes.2004

    • Author(s)
      Kawaji, K et al.
    • Journal Title

      Mol. Cell. Neurosci 25

      Pages: 228-240

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Oscillating Purkinje neuron activity causing involuntary eye movement in a mutant mouse deficient in the glutamate receptor δ2 subunit.2004

    • Author(s)
      Yoshida, T et al.
    • Journal Title

      J. Neurosci. 24

      Pages: 2440-2448

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Enhanced inhibitory synaptic transmission in the cerebellar molecular layer of the GluRδ2knockout mouse.2004

    • Author(s)
      Ohtsuki, G et al.
    • Journal Title

      J. Neurosci. 24

      Pages: 10900-10907

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Oscillating Purkinje neuron activity causing involuntary eye movement in a mutant mouse deficient in the glutamate receptor δ2 subunit.2004

    • Author(s)
      Yoshida T et al.
    • Journal Title

      J.Neurosci. 24

      Pages: 2440-2448

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Dual phases of migration of cerebellar granule cells guided by axonal and dendritic leading processes.2004

    • Author(s)
      Kawaji K et al.
    • Journal Title

      Mol.Cell.Neurosci. 25

      Pages: 228-240

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Regulation of dendritic maintenance and growth by a mammalian 7-pass transmembrane cadherin.2004

    • Author(s)
      Shima Y et al.
    • Journal Title

      Dev.Cell 7

      Pages: 205-216

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Enhanced inhibitory synaptic transmission in the cerebellar molecular layer of the GluRδ2 knockout mouse.2004

    • Author(s)
      Ohtsuki G et al.
    • Journal Title

      J.Neurosci. 24

      Pages: 10900-10907

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Long-term potentiation of mGluR1 activity by depolarization -induced Homer la in cerebellar Purkinje neurons.2003

    • Author(s)
      Minami, I et al.
    • Journal Title

      Eur. J. Neurosci. 17

      Pages: 1023-1032

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mechanism underlying cerebellar motor deficits due to mGluR1 -autoantibodies.2003

    • Author(s)
      Coesmans, M et al.
    • Journal Title

      Ann. Neurol. 53

      Pages: 325-336

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Direct interaction and functional coupling between metabotropic glutamate receptor subtype 1 and voltage-sensitive Ca v2.1 Ca^<2+> channel.2003

    • Author(s)
      Kitano, J et al.
    • Journal Title

      J. Biol. Chem. 278

      Pages: 25101-25108

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Long-term potentiation of mGluR1 activity by depolarization-induced Homerla in cerebellar Purkinje neurons.2003

    • Author(s)
      Minami, I et al.
    • Journal Title

      Eur. J. Neurosci. 17

      Pages: 1023-1032

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mechanism underlying cerebellar motor deficits due to mGluR1-autoantibodies.2003

    • Author(s)
      Coesmans, M et al.
    • Journal Title

      Ann.Neuro1. 53

      Pages: 325-336

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Direct interaction and functional coupling between metabotropic glutamate receptor subtype 1 and voltage-sensitive Cav2.1 Ca^<2+> channel.2003

    • Author(s)
      Kitano, J et al.
    • Journal Title

      J. Biol. Chem. 278

      Pages: 25101-25108

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Signaling cascade regulating long -term potentiation of GABA_A receptor responsiveness in cerebellar Purkinje neurons.2002

    • Author(s)
      Kawaguchi, S., Hirano, T.
    • Journal Title

      J. Neurosci. 22

      Pages: 3969-3976

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Delta/Notch-like epidermal growth factor (EGF) -related receptor,a novel EGF -like repeat-containing protein targeted to dendrites of developing and adultentral nervous systemneurons2002

    • Author(s)
      Eiraku, M et al.
    • Journal Title

      J. Biol. Chem. 277

      Pages: 25400-25407

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Calcineurin regulates induction of late phase of cerebellar long -term depression in rat cultured Purkinje neurons.2002

    • Author(s)
      Fujii, H., Hirano, T.
    • Journal Title

      Eur. J. Neurosci. 16

      Pages: 1777-1788

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Signaling cascade regulating long-term potentiation of GABAA receptor responsiveness in cerebellar Purkinje neurons.2002

    • Author(s)
      Kawaguchi, S., Hirano, T.
    • Journal Title

      J. Neurosci. 22

      Pages: 3969-3976

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Delta/Notch-like epidermal growth factor (EGF)-related receptor, a novel EGF-like repeat-containing protein targeted to dendrites of developing and adult central nervous system neurons.2002

    • Author(s)
      Eiraku, M et al.
    • Journal Title

      J. Biol. Chem. 277

      Pages: 25400-25407

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Calcineurin regulates induction of late phase of cerebellar long-term depression in rat cultured Purkinje neurons.2002

    • Author(s)
      Fujii, H., Hirano, T.
    • Journal Title

      Eur. J. Neurosci. 16

      Pages: 1777-1788

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Dynamic properties, interactions and adaptive modifications of vestibulo -ocular reflex and optokinetic response in mice.2001

    • Author(s)
      Iwashita, M et al.
    • Journal Title

      Neurosci. Res. 39

      Pages: 299-311

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Pax6 regulates granule cell polarization during parallel fiber formation in the developing cerebellum.2001

    • Author(s)
      Yamasaki, T et al.
    • Journal Title

      Development 128

      Pages: 3133-3144

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Dynamic properties, interactions and adaptive modifications of vestibulo-ocular reflex and optokinetic response in mice.2001

    • Author(s)
      Iwashita, M et al.
    • Journal Title

      Neurosci. Res. 39

      Pages: 299-311

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Brain and Mind2001

    • Author(s)
      Hirano, T.
    • Journal Title

      Tokyokagakudoujin 141

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Suppression of inhibitory synaptic potentiation by presynaptic activity through postsynaptic GABA_B receptors in a Purkinje neuron.2000

    • Author(s)
      Kawaguchi, S., Hirano, T.
    • Journal Title

      Neuron 27

      Pages: 339-347

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Roles of GABAergic inhibition and NMDA receptor subunits in the spatio -temporal integration in the cerebellar cortex of mice.2000

    • Author(s)
      Imamura, Y et al.
    • Journal Title

      Neurosci. Res. 38

      Pages: 289-301

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Suppression of inhibitory synaptic potentiation by presynaptic activity through postsynaptic GABAB receptors in a Purkinje neuron.2000

    • Author(s)
      Kawaguchi, S., Hirano
    • Journal Title

      Neuron 27

      Pages: 339-347

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Roles of GABAergic inhibition and NMDA receptor subunits in the spatio-temporal integration in the cerebellar cortex of mice.2000

    • Author(s)
      Imamura, Y et al.
    • Journal Title

      Neurosci. Res. 38

      Pages: 289-301

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 脳と心の正体2001

    • Author(s)
      平野 丈夫
    • Total Pages
      141
    • Publisher
      東京化学同人
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Minami, I et al.: "Long-term potentiation of mGluR1 activity by depolarization-induced Homerla in cerebellar Purkinje neurons."Eur.J.Neurosci.. 17. 1023-1032 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Coesmans, M. et al.: "Mechanism underlying cerebellar motor deficits due to mGluR1 -autoantibodies."Ann.Neurol.. 53. 325-336 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kitano, J. et al.: "Direct interaction and functional coupling between metabotropic glutamate receptor subtype 1 and voltage-sensitive Cav2.1 Ca^<2+> channel."J.Biol.Chem.. 278. 25101-25108 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Murai, N. et al.: "Vestibular compensation in glutamate receptor delta-2 subunit knockout mice : dynamic property of vestibule-ocular reflex."Eur.Arch.Oto-Rhino-Laryngol.. 65. 82-86 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kawaji, K. et al.: "Dual phases of migration of cerebellar granule cells guided by axonal and dendritic leading processes."Mol.Cell.Neurosci.. In Press.

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoshida, T. et al.: "Oscillating Purkinje Neuron Activity Causing Involuntary Eye Movement in a Mutant Mouse Deficient in the Glutamate Receptor δ2 Subunit"J.Neurosci.. In Press.

    • Related Report
      2003 Annual Research Report
  • [Publications] Fujii Hiroaki: "Calcium regulates induction of late phase of cerebellar long-term depression in rat cultured Purkinje neurons"European Journal of Neuroscience. 16. 1777-1788 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawaguchi Shin-ya: "Signaling cascade regulating long-term potentiation of GABA_A receptor responsiveness in cerebellar Purkinje neurons"Journal of Neuroscience. 22. 3969-3976 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Eiraku Mototsugu: "Delta/Notch-like epidermal growth factor (EGF)-related receptor, a novel EGF-like repeat-containing protein targeted dendrites of developing and adult central nervous system neurons"Journal of Biological Chemistry. 277. 25400-25407 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Minami Itsunari: "Long-term potentiation of mGluR1 activity by depolarization-induced homerla in cerebellar Purkinje neurons"European Journal of Neuroscience. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hirano Tomoo: "Roles of inhibitory interneurons in the cerebellar cortex"Annals of New Academy of Science. 978. 405-412 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamasaki, T.: "Pax6 regulates granule cell polarization during parallel fiber formation in the developing cerebellum"Development. 128. 3133-3144 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawaguchi, S.: "Signaling cascade regulating long-term potentiation of GABA_A receptor responsiveness in cerebellar Purkinje neurons"Journal of Neurosience. (発表予定).

    • Related Report
      2001 Annual Research Report
  • [Publications] Hirano, T.: "Roles of Inhibitory Interneurons in the Carebellar Cortex"Annaks of New York Academy of Sciences. (発表予定).

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawaguchi,S.: "Suppression of inhibitory synaptic potentiation by presynaptic activity through postsynaptic GABA^B receptors in a Purkinje neuron."Neuron. 27. 339-347 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Imamura,Y.: "Roles of GABAergic inhibition and NMDA receptor subunits in the spatio-temporal integration in the cerebellar cortex of mice."Neuroscience Research. 38. 289-301 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Iwashita,M.: "Dynamic properties, interactions and adaptive modifications of vestibulo-ocular reflex and optokinetic response in mice."Neuroscience Research. 39. 299-311 (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2001-04-01   Modified: 2018-03-28  

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