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Identification of signal transduction cascades involved in long-lasting potentiation of inhibitory synapses

Research Project

Project/Area Number 05454677
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Neuroscience in general
Research InstitutionJichi Medical School

Principal Investigator

KANO Masanobu  Faculty of Medicine, Jichi Medical School, Assistant, 医学部, 講師 (40185963)

Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1994: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1993: ¥4,800,000 (Direct Cost: ¥4,800,000)
Keywordscerebellar slice / patch clamp / inhibitory synapse / long-lasting potentiation / GABA receptor / Ca^<2+> / calmodulin-dependent kinase II / protein phosphatase / protein kinase G / protein kinase C / 遺伝子ノックアオウトマウス / calmodulin-dependent protein kinase II / パツチクランプ
Research Abstract

In cerebellar Purkinje cells, GABAergic inhibitory synaptic transmission undergoes long-lasting "rebound potentiation" following activation of excitatory climbing fiber iputs. Rebound potentiation is triggered by a climbing fiber-induced transient elevation of intracellular Ca^<2+> concentration, and is expressed as a long-lasting increase of postsynaptic GABA_A receptor sensitivity. In the present series of study, I found that inhibitors of the Ca^<2+>/calmodulin-dependent kinase II (CaM-KII) signal transduction pathway effectively block the induction of rebound potentiation. A non-selective protein kinase inhibitor, staurosporine, effectively blocked the induction of rebound potentiation. A calmodulin antagonist, calmidazolium, and a CaM-KII antagonist, KN-62, effectively blocked rebound potentiation, when they were applied extracellularly prior to and during Ca^<2+> channel activation. On the other hand, these antagonists had no effects on the once established rebound potentiation. … More Intracellular application of a peptide antagonist of CaM-KII also blocked the induction of rebound potentiation. These inhibitors had no effects on voltage-gated Ca^<2+> channel currents or on the basal inhibitory transmission itself. Furthermore, intracellular injection of active CaM-KII and application of a phosphatase inhibitor, calyculin A,induced enhancement of GABA_A receptor-mediated currents. These results strongly suggest that RP involves CaM-KII-mediated protein phosphorylation. The functional state of GABA_A receptors may be dependent on the balance between the phosphorylation by CaM-KII and the dephosphorylation by protein phosphatases.
I did not obtain the results that support involvement of other protein kinase cascades in rebound potentiation. As far as I examined, inhibitors of protein kinase A,protein kinase C and protein kinase G had no significant effects on rebound potentiation. The issues of involvement of these protein kinase cascades will be further studied using gene knockout mice. Less

Report

(4 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] A.Aiba,et al.: "Deficient cerebellar long-term depression and impaired motor learning in mGluR1 mutant mice." Cell. 79. 377-388 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Kano: "Long-lasting rebound potentiation of GABAergic inhibitorysynaptic currents in cerebellar purkinje cells." Biomed.Res.15,Suppl.l. 62-72 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Kano: "Calcium-induced long-lastin potentiation of GABAergic currents in cerebellar purkinje cells." Jpn J.physiol.44,Suppl.2. S131-S136 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Kano: "Plasticity of inhibitory synapses in brain:a possible memory mechanism that has been overlooked." Neurosci.Res.21. 177-182 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Kano,et al.: "Impaired synapse elimination dueing cerebellar development in PKCγ mutant mice." Cell. 83. 1223-1231 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] C.Chen,et al.: "Impaired motor coordination correlates with persistent multiple climbing fiber innervation in PKCγ mutant mice." Cell. 83. 1233-1242 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.kano,et al.: "Depolarization-induced calcium signals in the somata of cerebellar purinje neurons." Neurosci.Res.24. 87-95 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.kano,et al.: "Ryanodine receptor-mediated calcium release in rat cerebellar Purkinje neurones." J.Physiol.487. 1-16 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] F.Tempia,et al.: "The fractional calcium current through neuronal AMPA receptor channels with a'low'calcium permeability." J.Neurosci.15. 456-466 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 狩野 方伸,川合述史: "グルタミン酸レセプター." Clin.Neurosci.548-553 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 狩野 方伸: "佐藤昌康/編、ブレインサイエンス最前線95" 講談社サイエンティフィクス, 22-33 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] A.Aiba, et al.: "Deficient cerebellar long-term depression and impaired motor learning in mGluR1 mutant mice." Cell. 79. 377-388 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Kano: "Long-lasting rebound potentiation of GABAergic inhibitory synaptic currents in cerebellar Purkinje cells." Biomed.Res.15, Suppl.1. 62-72 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Kano: "Calcium-induced long-lasting potentiation of GABAergic currents in cerebellar Purkinje cells." Jpn.J.Physiol.44, Suppl.2. S131-S136 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Kano: "Plasticity of inhibitory synapses in the brain : a possible memory mechanism that has been overlooked." Neurosci.Res.21. 177-182 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Kano, et al.: "Impaired synapse elimination during cerebellar development in PKCgamma mutant mice." Cell. 83. 1223-1231 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] C.Chen, et al.: "Impaired motor coordination correlates with persistent multiple climbing fiber innervation in PKCgamma mutant mice." Cell. 83. 1233-1242 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Kano, et al.: "Depolarization-induced calcium signals in the somata of cerebellar Purkinje neurons." Neurosci.Res.24. 87-95 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Kano, et al.: "Ryanodine receptor-mediated calcium release in rat cerebellar Purkinje neurones." J.Physiol.487. 1-16 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] F.Tempia, et al.: "The fractional calcium current through neuronal AMPA receptor channels with a 'low 'calcium permeability." J.Neurosci.15. 456-466 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M. Kano et al.: "Impaired synapse elimination during cerebellar development in PKCγ mutant mice." Cell. 83. 1223-1231 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] C. Chen et al.: "Impaired motor coordination correlates with persistent multiple climbing fiber innervation in PKCγ mutant mice." Cell. 83. 1233-1242 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] M. Kano: "Plasticity of inhibitory synapses in the brain : a possible memory mechanism that has been overlooked." Neuroscience Research. 21. 177-182 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] M. Kano et al.: "Depolarization-induced calcium signals in the somata of cerebellar Purkinje neurons." Neuroscience Research. 24. 87-95 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] M. Kano et al.: "Ryanodine receptor-mediated calcium release in rat cerebellar Purkinje neurones." Journal of Physiology. 487. 1-16 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] F.Tempia et al.: "The fractional calcium currentthrough neuronal AMPA receptor channels with a ′low′ calcium permeablity." Journal of Neuroscience. 15. 456-466 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 狩野方伸,川合述史: "グルタミン酸レセプター" Clinical Neuroscience. 13. 548-553 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] A,Aiba et al.: "Deficient cerebellar long-term depression and impaired motor learning in mGluR1 mutant mice." Cell. 79. 377-388 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] M,Kano: "Long-lasting rebound potentiation of GABAergic inhibitory synaptic currents in cerebellar Purkinje cells" Biomedical Research. 15,Suppl.1. 62-72 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] M,Kano: "Calcium-induced long-lasting potentiation of GABAergic currents in cerebellar Purkinje cells" Japanese Journal of Physiology. 44,Suppl.2. S131-S136 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] M,Kano: "Plasticity of inhibitory synapses in the brain:a possible memory mechanism that has been overlooked" Neuroscience Research. 21. 177-182 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] M,Kano et al.: "Ryanodine receptor-mediated calcium release in rat cerebellar Purkinje neurones" Journal of Physiology. (in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 狩野 方伸: "佐藤昌康/編、ブレインサイエンス最前線95" 講談社サイエンティフィクス, 12 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] M.Kano: "Rebound potentiation of GAB Aergic inhibitory synaptic transmission in cerebellar Purkinje cells:its properties and possible mechanisms" Behavioral and Brain Sciences. (in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] M.Kano: "Long-lasting rebound potentiation of GAB Aergic inhibitory synaptic currents in cerebellar Purkinje cells" Biomedical Research. (in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] M.Kano: "Calcium-induced long-lasting potentiation of GAB Aergic curents in cerebellar Purkinje cells" Japanese Joumal of Physiology. (in press). (1994)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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