杏仁核、背側海馬與前額葉內側皮質在新近與久遠記憶的角色：PKMz與恐懼記憶的儲存

Roles of the Amygdala, Hippocampus and Medial Prefrontal Cortex in Recent and Remote Memory: PKMz and Storage of Fear Experience

劉品吾(Pin-Wu Liu)

指導教授 ： 梁庚辰

國立臺灣大學/理學院/心理學研究所/碩士(2015年)

https://doi.org/10.6342/NTU.2015.01237

摘要

記憶理論指出，新近形成的長期記憶會進一步穩固成永久記憶，新近記憶(recent memory)的神經表徵如何轉化成久遠記憶(remote memory)，是生理心理學家關切的議題。過去研究發現，杏仁核、海馬與前額葉皮質在許多恐懼相關學習作業中扮演重要角色。然而，這些腦區在新近與久遠記憶有無不同的角色並不清楚。由於新近與久遠記憶的轉化是在保存時距內進行，探討這問題需要能夠在記憶已經儲存後操弄記憶的神經痕跡。近期研究發現protein kinase M zeta (PKMz)為神經細胞內保持記憶儲存(memory storage)的重要蛋白質。本論文的研究為檢驗上述腦區在儲存情緒記憶的角色，於大白鼠習得抑制型躲避作業(inhibitory avoidance task, IA)或情境恐懼制約作業(contextual fear conditioning, CFC)後一天或二十天，於杏仁核、背側海馬與前額葉內側皮質注射PKMz特定抑制劑myristolated PKC zeta pseudosubstrate (ZIP)，以削弱存好的恐懼記憶。實驗結果發現，ZIP注入上述杏仁核與海馬僅損害抑制型躲避作業的新近記憶，不損害久遠記憶；ZIP在新近記憶形成後，注射在前額葉內側皮質對當時的記憶測試表現沒有影響，但在久遠記憶測試時出現損害。相對地，杏仁核內注射ZIP損害情境恐懼制約作業的新近記憶，不影響久遠記憶，前額葉內側皮質注射ZIP不影響任何記憶。上述結果顯示大白鼠自不同的學習作業所獲得的恐懼記憶，會根據學習內涵不同而有不同神經機制，PKMz在內涵互異的記憶歷程中具有不同的參與程度。

關鍵字

情緒 ； 記憶儲存 ； 系統穩固 ； 抑制型躲避學習作業 ； 情境恐懼制約作業

並列摘要

This study aims to understand the neural mechanisms underlying storage of fear memory and its update over time. The neural mechanism subserving consolidation of fear memory has been well documented, but little is known for storage maintenance of it. Previous evidence showed that inhibition of protein kinase M zeta (PKMz), which is proposed to support cellular changes for memory storage within the amygdala, dorsal hippocampus (DH) or medial prefrontal cortex (mPFC), impaired tasks involving fear, space or drug related information respectively. The inhibitory avoidance (IA) task and contextual fear conditioning (CFC) task are two different types of fear learning that respectively engaged instrumental or classical conditioning. However, the role of PKMz within these three areas in memory storage of the IA and CFC tasks remains unknown. To address this question, male Wistar rats with cannulae implanted in one of these areas were trained on either one-trial step-through IA task or two-phase training paradigm of CFC task. They were randomly assigned to receive a PKMz inhibitor - ZIP (10 nmole/ul) or vehicle infusion in different time points. The results showed that for IA task, intra-amygdala, -DH, or -mPFC infusion of ZIP one day after training impaired fear memory. For treatments in the amygdala and DH, the effect was apparent in the recent memory tests, but that in the mPFC was not apparent until the remote memory test. On the other hand, for the CFC task infusion of ZIP into the amygdala impaired recent memory, however, there was no such effect on memory when intra-mPFC infusion of ZIP. These findings suggest that fear memory would store in different brain regions according to different types of learning tasks. Further, PKMz may have different roles in different kinds of memory processes.

並列關鍵字

emotion ； memory storage ； system consolidation ； contextual fear conditioning ； inhibitory avoidance task

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