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Roles of GABA in the development of the nervous system : analysis of GAD-deficient mice

Research Project

Project/Area Number 13480269
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neuroscience in general
Research InstitutionOkazaki National Research Institutes

Principal Investigator

OBATA Kunihiko  Okazaki National Research Institutes, Physiology Institute, 生理学研究所, 教授 (60013976)

Co-Investigator(Kenkyū-buntansha) KANEKO Koichi  Okazaki National Research Institutes, Physiology Institute, 生理学研究所, 助手 (50194907)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥9,500,000 (Direct Cost: ¥9,500,000)
Fiscal Year 2002: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥6,100,000 (Direct Cost: ¥6,100,000)
KeywordsGABA / glutamic acid decarboxylase / knockout mouse / green fluorescent protein / superior colliculus / 神経発生 / 遺伝子改変マウス / 小脳 / 聴覚脳幹反応 / 恐怖条件反射
Research Abstract

γ-Aminobutyric acid (GABA) is synthesized from glutamate by two isoforms of glutamic acid decarboxylase (GAD), GAD65 and GAD67. In order to further elucidate the roles of GABA in the developing and mature brain, we have generated GAD gene-knockout mice and analyzed their phenotypes. While GAD65 is developed postnatally and its deficiency results in seizure and abnormal emotional behavior, expression of GAD67 starts simultaneously with differentiation of GABAergic neuron at an early embryonic stage. Development of GABAergic neurons was studied in the superior colliculus (SC) of the GAD67+/- and GFP+/- mice. Although the SC is layered structure as the neocortex, its GABAergic neurons were originated together with other neurons from the nearby ventricular zone. Before GABAergic neurons were differentiated in the SC, abundant GABAergic fibers were transiently present on the surface. They originated probably outside of SC and crossed the midline, suggesting their developmental roles. GAD67-/- mice contained less than 10% of GABA compared with the wild type but did not show any serious defect in their brain structure. Neural function of GAD67 knockout mice did not survive after birth because of cleft plate and their neural function could not studied in adult animals. When the brainstem isolated from the embryo or newborn was studied electrophyiologically, respiratory rhythm and inhibitory synaptic currents in respiratory neurons were greatly impaired.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] O Stork, S Stoke, HC Pepe, K Obata: "Identification of genes expressed in the amygdaladuring the formation of fear memory"Learning and Memory. 8. 209-219 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamagata Y, Jovanovic JN, Czemik AJ, Greengard P, Obata K: "Bidirectional changes in synapsin I phosphorylation at MAP kinase-dependent sites by acute neuronal excitation in vivo"J Neurochem. 80. 835-842 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Stork O, Ji FY, Obata K: "Reduction of extracellular GABA in the mouse amygdala during and following confrontation with a conditioned fear stimulus"Neurosci Lett. 327. 138-142 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Stork O, Kojima N, Stork S, Kume N, Obata K: "Resistance to alcohol withdrawal-induced behaviour in Fyn transgenic mice and its reversal by ifenprodil"Mol Brain Res. 105. 126-135 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Stork O, Yamanaka H, Stork S, Kume N, Obata K: "Altered conditioned fear behavior in glutamate decarboxylase 65 null mutant mice"Genes Brain Behav. 2. 65-70 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ebihara S, Obata K, Yanagawa Y: "Mouse vesicular GABA transporter gene : genomic organization transcriptional regulation and chromosomal localization"Mol Brain Res. 110. 126-139 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 柳川右千夫, 小幡邦彦: "バイオサイエンスの新世紀 第12巻 感覚器官と脳内情報処理"共立出版(御子柴克彦, 清水隆夫編). 250 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ebihara S, Obata K & Yanagawa Y.: "Mouse vesicular GABA transporter gene : genomic organization, transcript tional regulation and chromosomal localization"Mol Brain Res. 110. 126-139 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Stork O, Yamanaka H, Stork S, Kume N & Obata K.: "Altered conditioned fear behavior in glutamate decarboxylase 65 null mutant mice"Genes Brain Behav. 2. 65-70 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Stork O, Kojima N, Stork S, Kume N & Obata K.: "Resistance to alcohol withdrawal-induced behaviour in Fyn transgenic mice and its reversal by ife nprodil"Mol Brain Res. 105. 126-135 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Stork O, Ji FY & Obata K.: "Reduction of extracellular GABA in the mouse amygdala during and following confrontation with a conditioned fear stimulus"Neurosci Lett. 327. 128-142 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamagata Y, Jovanovic JN, Czernik AJ, Greengard P & Obata K.: "Bidirectional changes in synapsin I phosphorylation at MAP kinase-dependent sites by acute neuromal excitation in vivo"J Neurochem. 80. 835-842 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Stork O, Stork S, Pepe HC & Obata K.: "Identification of genes expressed in the amygdala during the formation, of fear memory"Learning and Memory. 8. 209-219 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamagata Y, Jovanovic JN, Czernik AJ, Greengard P, Obata K: "Bidirectional changes in synapsin I phosphorylation at MAP kinase-dependent sites by acute neuronal excitation in vivo"J Neurochem. 80. 835-842 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Stork O, Ji FY, Obata K: "Reduction of extracellular GABA in the mouse amygdala during and following confrontation with a conditioned fear stimulus"Neurosci Lett. 327. 138-142 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Stork O, Kojima N, Stork S, Kume N, Obata K: "Resistance to alcohol withdrawal-induced behaviour in Fyn transgenic mice and its reversal by ifenprodil"Mol Brain Res. 105. 126-135 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ebihara S, Obata K, Yanagawa Y: "Mouse vesicular GABA transporter gene : genomic organization, transcriptional regulation and chromosomal localization"Mol Brain Res. 110. 126-139 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Stork O, Yamanaka H, Stork S, Kume N, Obata K: "Altered conditioned fear behavior in glutamate decarboxylase 65 null mutant mice"Genes Brain Behav. 2. 1-6 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 小幡邦彦: "GABA合成酵素(GAD)ノックアウトマウスでみたGADとGABAの作用"脳と神経. 54. 1034-1040 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 柳川右千夫, 小幡邦彦: "感覚器官と脳内情報処理 7-8章GABAトランスポーター"共立出版(御子柴克彦・清水隆夫編). 260 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Stork 0, Stork S, Pape HC, Obata K: "Identification of Genes Expressed in the Amygdala During the Formation of Fear Memory"Learning & Memory. 8. 209-219 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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