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研究生:鍾妮均
研究生(外文):Ni-chun Chung
論文名稱:Alpha1HT型鈣離子通道基因剔除小鼠於情境痕跡恐懼記憶提取後海馬迴內基因表達
論文名稱(外文):Gene expression in the hippocampus of alpha1H T-type calcium channel knockout mice after retrieval of contextual trace fear conditioning
指導教授:劉怡均劉怡均引用關係
指導教授(外文):Ingrid Y.-C Liu
學位類別:碩士
校院名稱:慈濟大學
系所名稱:分子生物暨人類遺傳學研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
畢業學年度:98
語文別:英文
論文頁數:59
中文關鍵詞:學習記憶海馬迴α1H T型鈣離子通道基因剔除小鼠痕跡恐懼制約莫氏水迷宮微矩陣基因晶片
外文關鍵詞:Hippocampuslearning and memoryα1H T-type calcium channelKO micetrace fear conditioningMorris water mazemicroarray analysis
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電位依賴型 (voltage-dependent) 鈣離子通道的開啟會誘發許多細胞內生物化學的反應,例如肌肉的收縮、賀爾蒙或神經傳導物質的釋放、以及活化下游基因表達。海馬迴已知於情境及空間學習記憶上扮演一重要角色,而海馬迴各神經迴路皆有α1H T型鈣離子通道高度表達,因此我們假設此型鈣離子通道應於某種程度上參與了學習記憶的形成。本實驗室之前的研究已發現α1H T型鈣離子通道基因剔除小鼠在情境記憶上有學習不良的現象 (Jhe-Wei Shen, 2005),本篇研究論文中則發現這些基因剔除小鼠在另一種同樣依賴海馬迴學習模式,莫氏水迷宮 (Morris water maze) 中進行的測試後,表現出方向感學習正常。本論文因此進一步利用微矩陣基因晶片比較正常的野生型小鼠與α1H T型鈣離子通道基因剔除小鼠於接受情境痕跡恐懼記憶提取後,左右側海馬迴內基因表達是否有差異。結果顯示在接受情境線索刺激後,與從未接受訓練的對照組相比,正常的野生型小鼠的左、右側海馬迴之表達基因有側極化的現象,僅有少量基因會於左右側海馬迴呈現同樣的表達量。這些訓練後於野生型小鼠的左、右側海馬迴會呈現正調控或是負調控表達,卻於基因剔除小鼠的海馬迴中沒有改變的基因,可能是直接受到經由α1H T型鈣離子通道引入之鈣離子流調控的下游基因。功能性分類後,這些基因大多屬於執行神經活性的功能,也就是與神經塑型有高度相關性。此篇論文研究發現與野生型小鼠相比,α1H T型鈣離子通道基因剔除小鼠於方向感學習上表現正常,但在提取情境恐懼記憶時則有下游基因活化程度變異之情形,這些特異表達基因即可能是導致此種基因剔除小鼠輿情境記憶學習差異的原因。本研究顯示α1H T型鈣離子通道與方向記憶的形成及提取無關,但對於情境痕跡恐懼記憶的提取卻扮演著重要角色。
Voltage-dependent calcium channels (VDCC) trigger many intracellular biochemical events, including muscle contraction, gene expression or hormones and neurotransmitter secretion. Among all VDCCs, the T-type Ca2+ channel α1H subunit encoded by Cav3.2 gene is highly expressed in the hippocampus, which is correlated with contextual learning and spatial memory. Our previously research (Jhe-Wei Shen, 2005) showed that α1H KO mice are impaired in contextual trace fear conditioning, step-down and step-through avoidance tests but functionally normal in locomotor activity and auditory trace fear conditioning. Whether α1H T-type Ca2+ channels are also important to other hippocampal-dependent learning or not is still unknown. In this thesis, α1H KO mice were used to perform Morris water maze and their learning appeared to be normal. Besides, using genome wide microarray analysis for retrieval of contextual fear, asymmetrical gene expression patterns of bilateral hippocampi in training WT groups versus na��ve groups were observed. A cluster of genes that only revealed differential expression in WT group but not in KO group after contextual test may directly modulated by calcium influx via α1H T-type Ca2+ channels. Most of them are functionally related to neuronal activities and neural plasticity. My results showed that α1H KOs, though impaired in contextual fear conditioning, learned as well as WTs on spatial learning. In addition, differentially expressed genes had been screened clustered for retrieval of contextual fear. Some of them could be identified to be modulated by α1H T-type Ca2+ channels. My research indicates that α1H T-type Ca2+ channel independent with formation and retrieval of spatial learning but plays an important role in retrieving contextual trace fear conditioning.
Abstract I
中文摘要 II
Index III
Introduction 1
Aim 8
Materials and Methods 9
Results 15
Discussion 19
Figures 23
Tables 45
References 53
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