當環境事件刺激中樞神經系統後，學習歷程開始，並且中樞神經系統開始整合這些刺激訊號。這一段學習過程很快地會歷經一個假設性的穩固化過程並將此經驗儲存在中樞神經系統直到我們需要這段記憶的資訊而再次去提取。而記憶提取通常是為了添增新的資訊或是再強化這段記憶，很多實驗研究證明這過程會使這段記憶進入不穩定的狀態，隨後這不穩定狀態記憶會自發性地經歷一個假設性的再穩固階段，並再次使這記憶穩定地儲存在中樞神經系統中。本篇論文將探討獲取學習以及再穩固化這兩個階段。第一部分，我研究小鼠表現恐懼相關記憶上之性別差異是否在學習階段就不同，其相關機制又為何? 線索制約僵直反應、電生理記錄，以及蛋白質分析將用於探討這個議題。結果顯示母小鼠在線索制約僵直反應、杏仁核LTP表現、GluR1、GluR2，以及PSD-95蛋白表達量都高過公小鼠，而雄性激素可能主導了這些差異。第二部分，研究干擾一個記憶再穩固化歷程是否同時干擾其他沒被提取出來的記憶?在這章節，小鼠依序學習古柯鹼場地制約偏好學習記憶以及被動逃避學習記憶。提取被動逃避學習記憶(或場地制約偏好記憶)之後立刻在BLA施打蛋白質合成抑制劑(anisomycin)發現兩小時後被動逃避學習記憶(或場地制約偏好記憶)的再測試表現降低了。提取被動逃避學習記憶(或場地制約偏好記憶)之後立刻在CeA施打anisomycin發現兩小時後的被動逃避學習記憶(或場地制約偏好記憶)再測試表現雖沒被影響，但是在施打5天後的再測試被動逃避學習記憶(或場地制約偏好記憶)之表現降低了。如沒提取被動逃避(或場地制約偏好)的學習記憶或提取其他學習記憶，則無論在BLA或CeA施打蛋白質合成抑制劑都不影響被動逃避學習記憶(或場地制約偏好記憶)的表現。這樣的結果暗示著杏仁核涉及調控情緒相關記憶的再穩固化過程。而在情感相關的記憶再穩固化過程，BLA對於前期的記憶再穩固化重要，而CeA則在後期的記憶再穩固化扮演重要角色。在附錄部份，我研究記憶穩固化階段異常的記憶相關疾病，阿滋海默症。我假設β糊蛋白很可能跟血球上的蛋白質進行交互作用進而引發血管相關病症最後導致AD病症的加劇。我利用阿滋海默症基因轉殖小鼠來探討血紅素以及β糊蛋白在腦中的關係。結果顯示血紅素在阿滋海默症基因轉殖小鼠會如β糊蛋白隨著年紀變大而表達量上昇，β糊蛋白與血紅素β次單位在表達位置上有高度相關性。在海馬迴引發出血後，血紅素訊號會徵集β糊蛋白聚集。這結果暗示血紅素會幫助β糊蛋白堆積。

When environmental events or sensory stimuli impinge upon our central nervous system, we begin to learn (acquisition process) and central nervous system begins to integrate all the incoming information. Acquisition processes soon is placed by consolidation in an attempt to consolidate such information into the central nervous system until this acquired memory is stored and later retrieved under request. Retrieving an acquired memory turns this stable memory into a labile state for incorporation of new incoming information or strengthening this memory. Labile memory then, theoretically, undergoes a spontaneous reconsolidation process and being again stably stored in the central nervous system. In present studies, two of these processes, acquisition and reconsolidation, were discussed. In part 1, whether sex difference in performance of emotional related memories is different in acquisition process was investigated. And what are promising underlying mechanisms? Fear conditioning freezing behavior test, electrophysiology, and protein assay were used in this study. Female mice show higher magnitude in cue induced freezing, amygdaloid LTP performance, GluR1, GluR2, and PSD-95 protein level compare with male mice. Gonadal hormone in male mice may be responsible for sex difference of fear condition behavioral performance. In part 2, I investigated whether disturbance of one retrieved memory by inhibition of de novo protein synthesis during reconsolidation process is also affecting other non retrieved memory. Mice were trained to sequentially acquire both cocaine-induced conditioned place preference (CPP) and step-through passive avoidance (PA) memories. Immediately following PA/CPP retrieval, intra-BLA anisomycin infusion was found to decrease subsequent PA/CPP performance in retests. Immediately following PA/CPP retrieval, intra-CeA anisomycin infusion did not acutely affect PA/CPP performance but decreased such a PA/CPP memory 5 days later. When PA/CPP retrieval procedure was omitted, intra-BLA or intra-CeA anisomycin infusion did not affect PA/CPP memory. Intra-BLA and intra-CeA anisomycin infusion alone did not affect subsequent PA/CPP memory. These results, taken together, imply that de novo protein synthesis in amygdala plays an important role in modulating reconsolidation of emotion-related memory. More importantly, de novo protein synthesis in the BLA is essential for early phase reconsolidation of retrieved emotion-related memories. Protein synthesis in the CeA is required for late phase reconsolidation of retrieved emotion-related memories. In appendix, I discussed Alzheimer’s disease, a memory related disease, which was thought abnormal in consolidation process. I hypothesize that interaction between hemoglobin and β-amyloid in mini-hemorrhagic damaged brain may facilitate Alzheimer's disease development and progression. Male double (AP/PS, Amyloid precursor protein/ Presenilin) transgenic mice was used in this study. Hemoglobin was up regulation in alzheimer’s disease mice and hemoglobin β is correlation with β-amyloid. And in in vivo study, intra-hippocampus induction of hemorrhage induce hemoglobin leakage and recruit β-amyloid protein deposition suggesting that hemorrhage may enhance β-amyloid deposition.

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