| Project/Area Number |
10480229
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neuroscience in general
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| Research Institution | NATIONAL INSTITUTE FOR PHYSIOLOGICAL SCIENCES |
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Principal Investigator |
OBATA Kunihiko NATL.INST.PHYSIOL.SCI., PROF., 生理学研究所, 教授 (60013976)
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| Co-Investigator(Kenkyū-buntansha) |
KANEKO Kohichi NATL.INST.PHYSIOL.SCI., RES.ASSO., 生理学研究所, 助手 (50194907)
YANAGAWA Yuchio NATL.INST.PHYSIOL.SCI., ASSO.PROF., 生理学研究所, 助教授 (90202366)
MARUYAMA Kei NATL.INST.PHYSIOL.SCI., ASSO.PROF. (30211577)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥10,700,000 (Direct Cost: ¥10,700,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1999: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1998: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Keywords | GABA / glutamtic acid decarboxylase / gene targeting / mice / cleft palate / emotional behavior / amygdala / 情動 / けいれん / ガンマ・アミノ酪酸 / マウス / 神経発生 |
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| Research Abstract |
γ-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the mammalian central nervous system and synthesized by two isoforms of glutamic acid decarboxylase (GAD), GAD65 and GAD67. We produced GAD-deficient mice by homologous recombination and analyzed their brain for further elucidation of the roles of GABA.Brain GABA contents were reduced to 7% in the fetal and newborn GAD67-deficient mice and to 50-70% in the adult GAD65-deficient mice, indicating the importance of GAD67 at the fetal stage and GAD65 at postnatal maturation. Deletion of both isoforms did not induce any serious defects in brain structure. This finding does not support a current hypothesis that GABA is crucial for the neural histogenesis. GAD67-deficient mice showed cleft palate and abnormal activity of respiratory neural network. Adult GAD65-deficient mice showed the abnormality in every emotional behavior test, suggesting higher anxiety and abnormal fear response. Patch-clamp recording of synaptic activities in slice preparation revealed that spontaneous inhibitory transmission was reduced while the excitatory transmission was enhanced in the GAD65-deficient amygdala.
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