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題名：大鼠似情節記憶歷程裡海馬迴iCA1與內側前額葉扮演的角色
作者：洪旭慶
作者(外文)：Hsu-Ching Hung
校院名稱：國立中正大學
系所名稱：心理學研究所
指導教授：李季湜
學位類別：博士
出版日期：2015
主題關鍵詞：似情節記憶；內側前額葉皮質；海馬迴；恐懼制約；大鼠；episodic-like memory；medial prefrontal cortex；hippocampus；fear conditioning；rat
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情節記憶(episodic memory)是指人們有能力提取過去的經驗，並記得自己經歷過的事件是發生在什麼時間與地點。而動物展現出將事件、空間以及時間這三項訊息整合在一起的記憶能力稱為似情節記憶(episodic-like memory)。根據過去動物實驗的研究指出，大腦內側前額葉皮質(medial prefrontal cortex)與海馬迴(hippocampus)在形成似情節記憶的過程中扮演重要的角色。另一方面，神經解剖的證據指出從海馬迴iCA1到內側前額葉皮質之間，有一個通過前視丘(anterior thalamus)的連結而成的雙向迴路，而海馬迴iCA1與內側前額葉皮質之間並沒有跨腦區直接的神經連結。這二個腦區是以何種互動模式來形成似情節記憶，至今仍無明確結論，因此本研究將探究此議題。本研究採用O’Brien的作業，這一作業流程由三階段歷程來完成恐懼制約(fear conditioning)的似情節記憶：前探索階段形成時間與空間的配對連結(pair-assocation)；制約階段整合時間、空間與電擊事件而形成恐懼制約之似情節記憶；測試階段透過對空間的線索提取出似情節記憶。我們的實驗設計是在作業的不同階段使用利多卡因(lidocaine)暫時抑制內側前額葉皮質以及海馬迴iCA1，目的在找出這二腦區參與似情節記憶的關係。實驗一結果呈現在前探索與測試階段被暫時抑制雙側海馬迴iCA1的大鼠無法完成這項作業，我們推論似情節記憶歷程中形成時間與空間的連結以及提取似情節記憶需要海馬迴iCA1的參與。實驗二結果則是在制約與測試階段被暫時抑制雙側內側前額葉皮質的大鼠無法完成這項作業，我們推論似情節記憶歷程中事件、空間以及時間這三項訊息的整合以及提取似情節記憶是由內側前額葉皮質來完成。實驗三的結果發現暫時抑制同側(ipsilateral)腦半球內側前額葉皮質與海馬迴iCA1的大鼠能表現出似情節記憶的能力。我們推論只需要單一側腦半球的內側前額葉皮質與海馬迴iCA1共同運作就能完成似情節記憶。實驗四的結果則是在制約與測試階段被暫時抑制異側(contralateral)腦半球內側前額葉皮質與海馬迴的大鼠無法呈現似情節記憶的能力。我們推論似情節記憶的整合歷程以及提取歷程需要內側前額葉皮質和海馬迴iCA1共同參與。總結來說，本研究觀察到內側前額葉皮質與海馬迴分別參與似情節記憶歷程的不同階段，更進一步觀察到內側前額葉皮質與海馬迴形成的神經迴路共同參與似情節記憶能力的展現。
Episodic memory is the ability to consciously recollect specific events from one’s past personal experience including what happened in where and when. In animals, it focuses on the capability for combining these three main elements: “what”, “where” and “when”, to create “episodic-like memory”. Previous studies have shown that the medial prefrontal cortex and hippocampus may play an important role in the formation of episodic-like memory. Furthermore, anatomical evidence indicated that a reciprocal circuit connects the hippocampus iCA1 with mPFC via the anterior thalamus, while there is no direct neural connection between these two brain areas cross hemispheres. However, there is no clear conclusion about how the two areas interact in the processing of episodic-like memory. Thus, the present study intends to address this issue.We applied the O’Brien’s task to test episodic-like memory of a fear conditioning event in rats. The task comprises three stages: a when and where pair-association is formed in the pre-exposure stage; the combination of when, where, and the foot shock event is formed in the conditioning stage; the episodic-like memory is recalled through a spatial clue in the test stage. The experimental design of the present study is to temporarily deactivate mPFC and hippocampus iCA1 using lidocaine, and attempt to understand the roles of the two brain areas in episodic-like memory process.Results of experiment one showed that rats with temporary inhibition of bilateral hippocampus iCA1 in the pre-exposure and test stages failed in the task. We inferred that the processes of forming when-where connection and recalling episodic-like memory require involvement of hippocampus iCA1. In experiment two, we found that rats with temporary inhibition of bilateral mPFCin the conditioning and test stages failed in the task. Thus we inferred that the processes of integrating what-when-where connection and recalling episodic-like memory need involvement of mPFC. In experiment three, results showed that rats with temporary ipsilateral deactivationof mPFC and hippocampus iCA1 performed episodic-like memory task at the same level as the normal rats. It was interpreted that the processing of episodic-like memory requires the cooperation of intact mPFC and hippocampus iCA1 on at least one hemisphere of the brain. Results of experiment four showed that rats with contralateral deactivation of mPFC and hippocampus iCA1 in the conditioning and test stages showed deficits in processing episodic-like memory. Therefore, we inferred that the integrating and recalling processes of episodic-like memory requires the cooperation of mPFC and hippocampus iCA1. As a conclusion, this study found that mPFC and hippocampus iCA1 involves in different process of episodic-like memory respectively; and further, it was found that performing of episodic-like memory requires the cooperation of mPFC and hippocampus iCA1.
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