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研究生:陳明德
研究生(外文):Ming-Teh Chen
論文名稱:單側羥多巴胺破壞後清醒成鼠紋狀體神經元之細胞外電生理記錄
論文名稱(外文):In Vivo Extracellular Recording of Striatal Neurons in the Awake Rat Following Unilateral 6-Hydroxydopamine Lesions
指導教授:劉江川
指導教授(外文):Barry J. Hoffer
學位類別:博士
校院名稱:國防醫學院
系所名稱:醫學科學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2001
畢業學年度:90
語文別:中文
論文頁數:73
中文關鍵詞:基底核背側紋狀體多巴胺巴金森氏病整體紀錄
外文關鍵詞:basal gangliadorsal striatumdopamineParkinson's diseaseemsemble recording
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中文摘要
本實驗研究目的是進一步瞭解,背側紋狀體(dorsal striatum)之多巴胺傳入神經(dopaminergic input)的功能,以及比較在清醒與麻醉狀態下,多巴胺(Dopamine)破壞之影響。
應用長期植入的(chronically implanted)微電極(microwire electrode arrays),我們觀察可以自由活動的清醒大白鼠,在單側羥多巴胺 (6-hydroxydopamine; 6-OHDA)破壞上行多巴胺神經纖維束(ascending dopaminergic bundle)後,背側紋狀體神經元之放電特性(firing properties)。我們記錄注射阿朴嗎啡(apomorphine)後,在基準狀態下,以及在清醒與麻醉狀態下,紋狀體神經元之細胞外活動(extracellular activity)。以羥多巴胺破壞,同側大腦半球神經元之放電速度(firing rates),較對側未破壞神經元之放電速度快。Sham和未手術對照組,紋狀體之放電速度,較實驗組對側未破壞紋狀體之放電速度快。皮下注射阿朴嗎啡(0.05mg/kg),可增快在對側未破壞神經元之放電速度,同時減慢在同側破壞神經元之放電速度,因而縮小放電速度之差距。平均放電速度(mean firing rates)則是清醒動物較使用水化氯醛(chloral hydrate)麻醉動物為高,或許是因為麻醉會導致紋狀體神經元傳入神經之興奮性減少。水化氯醛麻醉會降低破壞,未破壞,和對照組紋狀體神經元放電速度,且程度相差不多,但是以羥多巴胺破壞組,紋狀體神經元之放電速度,仍較各組為快。單側羥多巴胺破壞會同時改變清醒動物之波峰輸出型態(the pattern of spike output),及造成每分鐘棘(bursts per minute)數目增加。阿朴嗎啡亦會改變波峰輸出型態,每分鐘棘,以及其他的棘參數(burst parameters)。
我們的發現顯示清醒動物多巴胺傳入神經損壞後之功能,是可以評估的。本研究提供一個新模式,可以測試減少或逆轉多巴胺細胞喪失之實驗,所導致的行為和功能改變。另外,這些結果建議:單側多巴胺破壞之動物模式中,對側紋狀體功能之改變,在評估實驗結果時,要列入考量。

英文摘要
The purpose of this study was to further understand the functional effects of dopaminergic input to the dorsal striatum, and to compare the effects of dopaminergic lesions in awake and anesthetized animals. We examined the effects of unilateral 6-hydroxydopamine (6-OHDA) lesions of the ascending dopaminergic bundle on the firing properties of dorsal striatal neurons in the awake freely-moving rat using chronically implanted microwire electrode arrays. We recorded extracellular activity of striatal neurons under baseline conditions and following the systemic injection of apomorphine in awake and anesthetized subjects. Firing rates were higher in the hemisphere ipsilateral to the 6-OHDA lesion as compared to rates of neurons from the contralateral unlesioned hemisphere. Striatal firing rates from sham and no-surgery control rats were, in general, higher than those from the contralateral unlesioned striatum of experimental subjects. Apomorphine (0.05 mg/kg, s.c.) normalized the differences in firing rates in lesioned animals by increasing firing of neurons within the contralateral unlesioned side, while simultaneously decreasing firing of neurons within the ipsilateral lesioned side. Mean firing rates were substantially higher in awake animals than in subjects anesthetized with chloral hydrate, perhaps reflecting anesthesia-induced decreases in excitatory input to striatal neurons. Chloral hydrate anesthesia decreased firing rates of neurons in the lesioned, unlesioned, and control striata to a similar degree, although absolute firing rates of neurons from the 6-OHDA-lesioned striata remained elevated over all other groups. Unilateral 6-OHDA lesions also altered the pattern of spike output in the awake animal as indicated by an increase in the number of bursts per minute following dopaminergic deafferentation. This and other burst parameters were altered by apomorphine. Our findings show that effects of dopaminergic deafferentation can be measured in the awake behaving animal, providing a new model for testing the behavioral and functional effects of experimental manipulations designed to reduce or reverse the effects of dopaminergic cell loss. In addition, these results suggest that the contralateral changes in striatal function which occur in the unilateral dopaminergic lesion model should be considered when evaluating experimental results.

1.單側羥多巴胺破壞後清醒成鼠紋狀體神經元之細胞外電生理記錄
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1.單側羥多巴胺破壞後清醒成鼠紋狀體神經元之細胞外電生理記錄
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2.在糖水補強反應工作事件中老鼠Nucleus Accumbens神經元信號
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附錄貳:本研究結果發表之文獻-----------------------------------------1.單側羥多巴胺破壞後清醒成鼠紋狀體神經元之細胞外電生理記錄
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第四章 討論------------------------------------------------------------------------------- 24
第五章 結論------------------------------------------------------------------------------- 33
第六章 參考文獻------------------------------------------------------------------------ 44
1.單側羥多巴胺破壞後清醒成鼠紋狀體神經元之細胞外電生理記錄
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1.單側羥多巴胺破壞後清醒成鼠紋狀體神經元之細胞外電生理記錄
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第二章 材料與方法--------------------------------------------------------------------- 52
第三章 結果------------------------------------------------------------------------------- 57
第四章 討論------------------------------------------------------------------------------- 61
第五章 結論------------------------------------------------------------------------------- 64
第六章 參考文獻------------------------------------------------------------------------ 71
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第六章 參考文獻
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