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Basic mechanisms of transmission in neuronal network

Research Project

Project/Area Number 14570903
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionHirosaki University

Principal Investigator

WADA Kazumaru  Hirosaki University, School of Medicine, Professor, 医学部, 教授 (60241486)

Co-Investigator(Kenkyū-buntansha) KANEKO Sunao  Hirosaki University, School of Medicine, Professor, 医学部, 教授 (40106852)
OKADA Motohiro  Hirosaki University, University Hospital, Lecturer, 医学部附属病院, 講師 (10281916)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 2003: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 2002: ¥2,700,000 (Direct Cost: ¥2,700,000)
KeywordsEpilepsy / mood disorder / SNARE / calcium channel / exocytosis / synprint / glutamate / GABA
Research Abstract

To clarify the etiology of functional neurotransmission disorders in central nervous system, we have studied the transmission mechanism in the temporoammonic pathway. In the first step, we determined interaction among GABAA, AMPA/glutamate receptors and protein kinases (PKA and PKC) in the exocytosis of GABA and glutamate using multiprobe microdialysis, as well as propagation of neuronal excitability using optical recording in the EC-Hippocampal formation. Multiprobe microdialysis demonstrated that EC-evoked GABA release in ventral CA1 was predominantly regulated by the PKC-related rather than PKA-related exocytosis mechanism and was augmented by the activation of glutamatergic transmission. Contrary to GABA release, EC-evoked glutamate release was predominantly regulated by PKA related rather than PKC-related mechanisms and was suppressed by activation of GABAergic transmission. Optical recording demonstrated that there are two sub-pathways in the temporoammonic pathway ; direct proje … More cts from EC layers (II-IV) to dendrites on pyramidal cells and GABAergic interneurons in ventral hippocampal CA1. PKC activation enhanced trisynaptic transmission, whether the GABAA receptor was functional or blocked, whereas PKC activation enhanced and inhibited temporoammonic transmission when the GABAA receptor was functional and blocked, respectively. Thus, GABAergic inhibition, which is regulated by PKC activity, in the temporoammonic pathway is more significant than that in the trisynaptic pathway. In the next step, we studied the effects of adaptor-protein on neurotransmission in the temporoammonic pathway using adaptor-protein type 3B (AP-3B) deficient mice. AP-3B deficient mice suffered from spontaneous epileptic seizures. Biochemical studies demonstrated the impairment of GABA release because of, at least in part, the reduction of vesicular GABA transporter in AP-3B deficient mice. This facilitated the induction of long-term potentiation in the hippocampus and the abnormal propagation of neuronal excitability via the temporoammonic pathway. Thus, AP-3B plays a critical role in the normal formation and function of a subset of synaptic vesicles. This work adds a new aspect to the pathogenesis of epilepsy. Less

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (26 results)

All 2004 Other

All Journal Article (17 results) Publications (9 results)

  • [Journal Article] Defective function of GABA-containing synaptic vesicles in mice lacking the AP-3B clathrin adaptor.2004

    • Author(s)
      Nakatsu F.et al.
    • Journal Title

      J Cell Biol. 167・2

      Pages: 293-302

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Marital status of patients with epilepsy with special reference to the influence of epileptic seizures on the patient's married life.2004

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

      Epilepsia 45・8

      Pages: 33-36

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Protein kinase associated with gating and closing transmission mechanisms in temporoammonic pathway.2004

    • Author(s)
      Okada M.et al.
    • Journal Title

      Neuropharmacology 47・4

      Pages: 485-504

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Physical and psychomotor development in the offspring born to mothers with epilepsy.2004

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

      Epilepsia 45・8

      Pages: 53-57

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Hyperactivity of endoplasmic reticulum associated exocytosis mechanism contributes to acute phencyclidine intoxication2004

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

      J Pharmacol Sci 95・2

      Pages: 214-227

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Both 3,4-dihydroxyphenylalanine and dopamine releases are regulated by Ca2+-induced Ca2+ releasing system in rat striatum2004

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

      Neurosci Lett 362・3

      Pages: 244-248

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Determination of exocytosis mechanisms of DOPA in rat striatum using in vivo microdialysis2004

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

      Neurosci Lett 36・7

      Pages: 241-245

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Pharmacological discrimination of protein kinase associated exocytosis mechanisms between dopamine and 3,4-dihydroxyphenylalanine in rat striatum using in vivo microdialysis2004

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

      Neurosci Lett 363・2

      Pages: 120-124

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Defective function of GABA-containing synaptic vesicles in mice lacking the AP-3B clathrin adaptor.2004

    • Author(s)
      Nakatsu F. et al.
    • Journal Title

      J Cell Biol. 167-2

      Pages: 293-302

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Marital status of patients with epilepsy with special reference to the influence of epileptic seizures on the patient's married life.2004

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

      Epilepsia 45-8

      Pages: 33-36

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Protein kinase associated with gating and closing transmission mechanisms in temporoammonic pathway.2004

    • Author(s)
      Okada M. et al.
    • Journal Title

      Neuropharmacology 47-4

      Pages: 485-504

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Physical and psychomotor development in the offspring born to mothers with epilepsy.2004

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

      Epilepsia 45-8

      Pages: 53-57

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hyperactivity of endoplasmic reticulum associated exocytosis mechanism contributes to acute phencyclidine intoxication2004

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

      J Pharmacol Sci 95-2

      Pages: 214-227

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Determination of exocytosis mechanisms of DOPA In rat striatum using in vivo microdialysis2004

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

      Neurosci Lett 367-2

      Pages: 241-245

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Both 3,4-dihydroxyphenylalanine and dopamine releases are regulated by Ca2+-induced Ca2+ releasing system in rat striatum2004

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

      Neurosci Lett 362-3

      Pages: 244-248

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Pharmacological discrimination of protein kinase associated exocytosis mechanisms between dopamine and 3,4-dihydroxyphenylalanine in rat striatum using in vivo microdialysis2004

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

      Neurosci Lett 363-2

      Pages: 120-124

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Determination of exocytosis mechanisms of DOPA in rat striatum using in vivo microdialysis2004

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

      Neurosci Lett 367・2

      Pages: 241-245

    • Related Report
      2004 Annual Research Report
  • [Publications] Okada M., et al.: "Age-dependent modulation of hippocampal excitability by KCNQ-channels"Epilepsy Res.. 53. 81-94 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hirose S., et al.: "The genetics of febrile seizures and related epilepsy syndromes"Brain Dev.. 25・5. 304-312 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Okada M., et al.: "Protein kinase associated with gating and closing transmission mechanisms in temporoammonic pathway"Neuropharmacology. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Okada M. et al.: "Age-dependent modulation of hippocampal excitability by KCNQ-channels"Epilepsy Res.. 53・1. 81-94 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hirose S. et al.: "Molecular genetics of human familial epilepsy syndromes"Epilepsia. 43・9. 9-21 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Okada M. et al.: "Exocytosis mechanism as a new targeting site for mechanisms of action of antiepileptic drugs"Life Sci. 72・4. 465-473 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Okada M. et al.: "Impaired M-current and neuronal excitability"Epilepsia. 43・9. 36-38 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kaneko S. et al.: "Genetic identifiers of epilepsy"Epilepsia. 43・9. 16-20 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kaneko S. et al.: "Genetics of epilepsy : current status and perspectives"Neurosci Res.. 44・1. 11-30 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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