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Molecular and cellular mechanisms of defective neural network rhythm generation

Research Project

Project/Area Number 15300128
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionNational Institute for Physiological Sciences (2004)
Okazaki National Research Institutes (2003)

Principal Investigator

IMOTO Keiji  National Institute for Physiological Sciences, Department of Information Physiology, Professor, 生体情報研究系, 教授 (00176512)

Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥15,900,000 (Direct Cost: ¥15,900,000)
Fiscal Year 2004: ¥7,900,000 (Direct Cost: ¥7,900,000)
Fiscal Year 2003: ¥8,000,000 (Direct Cost: ¥8,000,000)
Keywordsmutant mice / epilepsy / thalamus / neural network / patch-clamp / in vivo recording / rhythm synchronization / ion channel / モデル動物 / 多電極細胞外電位測定装置 / 視床大脳皮質投射
Research Abstract

In this project, we mainly tried to analyze network mechanisms in the hippocampus, thalamus, cerebral cortex and cerebellar cortex, which underlie neurological symptoms such as epilepsy and cerebellar ataxia, using spontaneous mutant neurological mice.
We identified a defect in the feedforward circuit of the thalamocortical projection in epileptic calcium channel mutant mice 'tottering'. We demonstrated the defect of synaptic transmission appears in a development-dependent manner. We tried to detect epileptiform discharges using a multi-electrode extracellular recording system, but we failed to obtain stable and consistent results.
Until recently, patch clamp recordings from brain slice preparations are mostly from single neurons. Because it is difficult to understand activity of the local network, we started to double- and triple-patch clamp recordings. With this advanced system, we elucidated the basic neural wiring pattern that is required for synchronized activity of thalamic neurons (manuscript in preparation).
We were also interested in the morphological impacts of calcium channel mutations. We used retrograde labeling of Purkinje neurons, and developed analysis software to quantitatively measure the territory and branching of Purkinje cell dendritic arbors. In addition to in vitro brain slice recordings, it is essential to record neural activity in vivo. We developed a system for in vivo recording. We are now making comparison between normal and mutant mice.

Report

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

    (14 results)

All 2005 2004 2003 Other

All Journal Article (12 results) Publications (2 results)

  • [Journal Article] Clinical and electrophysiological characterisrics of Brugada syndrome caused by a missense in the S5-pore site of SCN5A.2005

    • Author(s)
      Itoh H, Shimizu M, Mabuchi H, Imoto K
    • Journal Title

      J. of Cardiovascular Electrophysiology 16

      Pages: 378-393

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A novel missense mutation in the SCN5A gene associated with Brugada syndrome bid irectionally affecting blocking actions of antiarrhythmic drugs.2005

    • Author(s)
      Itoh H, Shimizu M, Tanaka S, Mabichi H, Imoto G
    • Journal Title

      J. of Cardiovascular 16

      Pages: 486-493

    • NAID

      10014384040

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Clinical and electrophysiological characteristics of Brugada syndrome caused by a missense mutation in the S5-pore site of SCN5A.2005

    • Author(s)
      Itoh H, Shimizu M, Mabuchi H, Imoto K
    • Journal Title

      J. of Cardiovascular Electrophysiology 16

      Pages: 378-383

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A novel missense mutation in the SCN5A gene associated with Brugada syndrome bidirectionally affecting blocking actions of antiarrhythmic drugs.2005

    • Author(s)
      Itoh H, Shimizu M, Tanaka S, Mabuchi H, Imoto K
    • Journal Title

      J. of Cardiovascular Electrophysiology 16

      Pages: 486-493

    • NAID

      10014384040

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Polyglutamine repearts of spinocerebellar ataxia 6 impair the cell-death-preventing effect of Cav2. 1 Ca^<2+> --- loss-of-function cellular model of SCA6.2004

    • Author(s)
      Matsuyama Z, Yanagisawa NK, Aoki Y, Black JL 3rd, Lennon VA, Mori Y, Imoto K, Inuzuka T
    • Journal Title

      Neurobiology of Disease 17

      Pages: 198-204

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Polyglutamine repeats of spinocerebellar ataxia 6 impair the cell-death-preventing effect of Cav2.1 Ca2+ channel ---loss-of-function cellular model of SCA6.2004

    • Author(s)
      Matsuyama Z, Yanagisawa NK, Aoki Y, Black JL 3rd, Lennon VA, Mori Y, Imoto K, Inuzuka T
    • Journal Title

      Neurobiology of Disease 17

      Pages: 198-204

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Polyglutamine repeats of spinocerebellar ataxia 6 impair the cell-death-preventing effec of Ca_v2.1 Ca^<2+> channel --- loss-of-function cellular model of SCA6.2004

    • Author(s)
      Matsuyama Z, Yanagisawa NK, Aoki Y, Black JL 3rd, Lennon VA, Mori Y, Imoto K, Inuzuka T
    • Journal Title

      Neurobiology of Disease 17

      Pages: 198-204

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Regulatory interaction of sodium channel IQ-motif with calmodulin C-terminal lobe.2003

    • Author(s)
      Mori M, Konno T, Morii T, Nagayama K, Imoto K
    • Journal Title

      Biochem Biophys Res Comm 307

      Pages: 290-296

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Stable expression and characterization of human PN1 and PN3 sodium channels.2003

    • Author(s)
      Akiba I, Seki T, Mori M, Iizuka M, Nishimura S, Sasaki S, Imoto K, Barsoumian EL
    • Journal Title

      Receptors Ohannels 9

      Pages: 291-299

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Barsoumian EL Stable expression and characterization of human PN1 and PN3 sodium channels.2003

    • Author(s)
      Akiba I, Seki T, Mori M, Iizuka M, Nishimura S, Sasaki S, Imoto K
    • Journal Title

      Receptors Channels 9

      Pages: 291-299

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Clinical and electrophysiological characteristics of Brugada syndrome caused by a missense mutation in the S5-pore site of SCN5A.

    • Author(s)
      Itoh H, Shimizu M, Mabuchi H, Imoto K
    • Journal Title

      J.of Cardiovascular Electrophysiology (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A novel missense mutation in the SCN5A gene associated with Brugada syndrome bidirectionally affecting blocking actions of antiarrhythmic drugs.

    • Author(s)
      Itoh H, Shimizu M, Tanaka S, Mabuchi H, Imoto K
    • Journal Title

      J.of Cardiovascular Electrophysiology (in press)

    • NAID

      10014384040

    • Related Report
      2004 Annual Research Report
  • [Publications] Mori M, Konno T, Morii T, Nagayama K, Imoto K: "Regulatory interaction of sodium channel IQ-motif with calmodulin C-terminal lobe."Biochem Biophys Res Comm. 307. 290-296 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Akiba I, Seki T, Mori M, Iizuka M, Nishimura S, Sasaki S, Imoto K, Barsoumian EL: "Stable expression and characterization of human PN1 and PN3 sodium channels."Receptors Channels. 9. 291-299 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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