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Physiological and morphological studies on cerebellar synapses of CaV2.1 mutant mice rocker
https://ir.soken.ac.jp/records/1181
https://ir.soken.ac.jp/records/1181444f7c98-f9c0-4677-ab31-bd797481068d
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要旨・審査要旨 (195.8 kB)
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本文 (19.7 MB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2010-02-22 | |||||
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タイトル | Physiological and morphological studies on cerebellar synapses of CaV2.1 mutant mice rocker | |||||
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タイトル | Physiological and morphological studies on cerebellar synapses of CaV2.2 mutant mice rocker | |||||
言語 | en | |||||
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言語 | eng | |||||
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資源タイプ識別子 | http://purl.org/coar/resource_type/c_46ec | |||||
資源タイプ | thesis | |||||
著者名 |
児玉, 貴史
× 児玉, 貴史 |
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フリガナ |
コダマ, タカシ
× コダマ, タカシ |
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著者 |
KODAMA, Takashi
× KODAMA, Takashi |
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学位授与機関 | ||||||
学位授与機関名 | 総合研究大学院大学 | |||||
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学位名 | 博士(理学) | |||||
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内容記述タイプ | Other | |||||
内容記述 | 総研大甲第1010号 | |||||
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値 | 生命科学研究科 | |||||
専攻 | ||||||
値 | 20 生理科学専攻 | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2006-09-29 | |||||
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値 | 2006 | |||||
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内容記述タイプ | Other | |||||
内容記述 | The rocker mice are hereditary ataxic mutants, which carry a point mutation in the gene<br />encoding the Ca<sub>V</sub> 2.1 (P/Q-type) Ca<sup>2+</sup> channel α1 subunit. They show the mildest<br />phenotypes among the reported Ca<sub>V</sub> 2.1 mutant mice, allowing us to evaluate primary<br />symptoms caused by the Ca<sub>V</sub> 2.1 dysfunction. Although the basic properties of the<br />rocker mutant channel have been reported, their influence on physiological functions<br />remains unclear. Here, I studied the impacts of the rocker mutant Ca<sup>2+</sup> channel on<br />synaptic transmission especially in cerebellar Purkinje cells, where Ca<sub>V</sub> 2.1 Ca<sup>2+</sup> channel<br />mediates a major activity-dependent Ca<sup>2+</sup> influx. Despite of the small changes in<br />channel function, synaptic transmission in the parallel fiber (PF)-Purkinje cell (PC)<br />synapses was severely impaired, whereas the climbing fiber inputs onto PCs appeared to function normally. I further explored the origin of the transmission impairment in the<br />PF-PC synapses in rocker mice. Presynaptic functions of the PF-PC synapses, however,<br />were unexpectedly normal in terms of paired-pulse facilitation, sensitivity to<br />extracellular Ca<sup>2+</sup> concentration, and glutamate concentration in synaptic clefts.<br />Electron microscopic analyses including freeze-fracture replica labeling revealed that<br />both the number and density of postsynaptic AMPA<br />(α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors substantially<br />decreased without gross structural changes of the PF-PC synapses. I also observed an<br />abnormal arborization of PC dendrites in young adult rocker mice (「1 month of age).<br />These lines of evidence suggest that the rocker mutation exerts its influence especially<br />on postsynaptic structures and functions in the PF-PC synapses. | |||||
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値 | 有 |