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研究生:李佳靜
研究生(外文):Chia-Ching Lee
論文名稱:恐懼記憶消除機制之探討
論文名稱(外文):Quenching of Fear Memory
指導教授:簡伯武簡伯武引用關係
指導教授(外文):Po-Wu Gean
學位類別:碩士
校院名稱:國立成功大學
系所名稱:藥理學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:中文
論文頁數:114
中文關鍵詞:突觸塑性長期抑制扁桃體恐懼記憶記憶消除磷酸酶低頻電刺激
外文關鍵詞:low-frequency stimulationquenchingmitogen-activated protein kinase ( MAPK )amygdalalong-term potentiationneuroplasticityDCG-IVlong-term depression
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中 文 摘 要

「記憶」是大腦重要的功能之一,關係著學習與創造的能力,而關於大腦形成記憶的機制及部位,一直都是難解的問題。拜近代科學之福,在行為模式及細胞分子研究的幫助下,得以探討細胞內極細微的變化,也漸漸解開了記憶這個迷團。在壓力沉重的現代社會,情緒記憶也日漸受重視,目前的研究認為發生的部位是邊緣系統�堛漱兮洢颾褋憿A當這區域接收到外界的刺激,突觸便會發生長期增益的現象,調控細胞內磷酸酶,進而影響細胞核的表現形成情緒記憶。

本篇的研究主要是探討長期抑制現象所導致的記憶消除現象(quenching),首先比較產生恐懼記憶的老鼠和正常老鼠其體外中樞扁桃體的表現。實驗結果發現老鼠雖然經過恐懼記憶的訓練,但是其長期增益現象和長期抑制現象的表現與正常老鼠並無明顯差異。接著進一步以活體探討中樞扁桃體突觸塑性的表現,我們發現以低頻電刺激及DCG-IV都可誘發長期抑制現象,並且造成老鼠的恐懼記憶消失的表現。同時,以西方點墨法觀察在形成記憶的過程中佔有重要地位的磷酸酶,證實Akt和MAPK也參與了記憶消除的機制。為觀察記憶消除的過程是否需要calcineruin的參與,我們加入cyclosporin A去抑制calcineruin的活性,發現低頻電刺激所導致的記憶消除現象也被抑制住;但cyclosporin A無法抑制DCG-IV所造成的記憶消除現象,顯示這兩者在形成記憶消失的機制上不盡相同。
Abstract in English

The amygdala has been suggested to play important role in certain forms of neuroplasticity such as emotional memory. If fear memory is encoded by a long-term potentiation ( LTP ) of synaptic transmission in the amygdala, then reversal of LTP in this area of the brain should provide an important mechanism for amelioration of anxiety and post-traumatic stress disorder.

Here we show that bilateral administration of low-frequency stimulation ( LFS ) to the external capsule ( EC ) or lateral nucleus of the amygdala ( LA ) in vivo can inhibit the expression of fear memory measured with fear-potentiated startle paradigm, a phenomenon termed quenching. Systemic injection of cyclosporin A, an immunosuppressant which inhibits calcineurin activity, dose-dependently prevents quenching. Fear conditioning-induced phosphorylation of Akt and mitogen-activated protein kinase ( MAPK ) is reduced by LFS treatment which is accompanied by an increase in the expression of calcineurin. However, the results that used DCG-IV by previous protocols are different, the activity and quantity of calcineurin is not increase. In view of the result, LFS quenching and DCG-IV quenching, underline differential cellular mechanisms.

This study characterizes the properties of LFS elicited quenching in amygdala and suggests an involvement of calcineurin cascade, and DCG-IV elicited quenching in amygdala does not require the activation of calcineurin in synaptic plasticity and memory storage.
中文摘要…………………………………………… 1
英文摘要…………………………………………… 4
縮寫檢索表………………………………………… 7
第一章 簡介……………………………………… 10
第二章 研究方法及實驗材料…………………… 26
第一節 腦切片之製作…………………… 27
第二節 恐懼老鼠動物模式……………… 28
第三節 細胞外電氣生理活性記錄法…… 28
第四節 手術和消除……………………… 29
第五節 西方點墨………………………… 31
第六節 鈣離子依賴型去磷酸酶活性測定法 37
第七節 實驗藥品來源…………………… 38
第八節 藥物的作用以及藥品配製……… 39
第九節 統計分析………………………… 40
第三章 對正常的老鼠與恐懼記憶的老鼠其中樞扁桃體神經
在體外的突觸傳遞訊席之探討…………… 45
第一節 實驗結果 (Results)…………… 46
第二節 討論 (Discussion)……………… 52
第四章 利用低頻電刺激( LFS )來探討恐懼消除之機制…59
第一節 序論 (Introduction)…………… 60
第二節 實驗結果 (Results)…………… 61
第三節 討論 (Discussion)……………… 67
第五章 利用GroupII metabotropic受體作用劑(DCG-IV)
來探討恐懼記憶消除之機制遞…………… 77
第一節 實驗結果(Results)……………… 78
第二節 討論 (Discussion)……………… 85
第六章 結論………………………………………… 94
參考文獻……………………………………………… 98
圖表索引……………………………………………… 111
參考文獻
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