透過您的圖書館登入
IP:18.223.106.232
  • 學位論文

以抑制型逃避作業探討大鼠腦部在習得與提取新近或久遠記憶時之c-Fos表現

c-Fos Expression in Rat’s brain Following Acquisition and Expression of Recent or Remote Memory in an Inhibitory Avoidance Task

指導教授 : 梁庚辰

摘要


抑制型逃避作業長久以來廣為被利用於研究學習與記憶的神經機制。大量的藥物操弄或區域毀除研究都發現,此種記憶的習得或表現涉及腦中多重神經結構的參與,以及這些腦部結構彼此的交互作用。然而這類的研究卻往往無法一次追蹤分散各處的記憶痕跡,並直接探究此些記憶痕跡彼此的可能關係。因此本研究利用早期立即基因的產物蛋白c-Fos作為神經活動的標記物,探討大鼠在學習抑制型逃避作業與提起其新近或久遠記憶時,各腦區間的活性關係,並進一步追尋記憶痕跡在時間向度上所展現的動態變化。結果發現,習得情境與電擊聯結的動物相較於單純經歷情境或經歷電擊的控制組,在特定腦區上展現出獨特的活動情形。其中杏仁核基底核區與背側海馬在記憶習得與新近或久遠記憶提取上都會活化;腦島皮質則在習得與提取久遠記憶時有高度活性。前額葉皮質內側的前邊緣皮質與前扣帶迴皮質不論在新近與久遠記憶提取上都有高活性表現;內膈核與依核則只針對久遠記憶有高度神經活動;而杏仁核中央核區與初級運動皮質在各時期都無顯著的活性提升。此外,本研究進行行為表現與神經活性的相關分析,發現學習之後短期記憶的表現與海馬的神經活性有高度相關;而新近與久遠記憶的提取表現則與海馬、杏仁核、其他皮質與皮質下區域的神經活動都呈現高度相關。

並列摘要


The inhibitory avoidance (IA) task is a widely adopted task to assess emotional memory. Accumulating data from pharmacological and other research have shown that acquisition and expression of such memory involved multiple brain regions as well as complicated interaction among them. However, findings from manipulative or electrophysiological recording studies fall short of tracing the full distribution of relevant sites for such learning. To investigate the neural substrates participating in IA learning and potential dynamic reorganization of brain regions involved in recent and remote memories, we tracked down the expression of protein c-Fos, the product of immediate-early gene c-fos, following acquisition, 1 day recall, and 30 day recall of IA memory in multiple brain regions implicated in the IA task. Separate groups of male Wistar rats were trained with context-exposure (C), shock-exposure (S) or context-shock association (IA) in the IA task and tested for memory 50 minutes, 1 day, or 30 days later. One hour after completion of training or testing, rats were perfused transcardially. Brain slices were prepared for c-Fos immunohistochemistry and c-Fos expression was measured in several brain regions implicated in memory formation and retrieval. Compared with the control group only exposed to context or shock, trained rats had increased c-Fos immunoreactivity in the basolateral amygdala and dorsal hippocampus following acquisition, recent or remote recall. In the insular cortex, increased c-Fos expression was observed after acquisition and remote recall. In the medial prefrontal cortex, increased c-Fos was found in prelimbic and cingulate cortex following either recent or remote recall. In contrast, in the medial septal area and nucleus accumbens, c-Fos was increased only following remote recall. No significance difference in c-Fos expression were found between trained rats and controls in the central amygdala and primary motor cortex. An additional correlative analysis further revealed significant high correlation in the CA1 and DG in the acquisition of IA memory. In recent memory recall, significant correlation was found in the BLA, CA1, DG, PrL, M1, and MSA. In remote memory recall, high correlation between the retention performance and c-Fos expression was found in extensive brain regions, including the BLA, CA1, CA3, DG, PrL, Cg1, M1, IC, MSA, and NAcc. These findings suggest a dynamic change of activated brain regions subserving the IA memory over the period from shortly after acquisition to remote retention.

參考文獻


Liang, K. C. (2009). Involvement of the amygdala and its connected structures in formation and expression of inhibitory avoidance memory: Issues and implications. Chinese Journal of Physiology, 52(4), 196-214.
Alden, M., Besson, J. M., & Bernard, J. F. (1994). Organization of the Efferent Projections from the Pontine Parabrachial Area to the Bed Nucleus of the Stria Terminalis and Neighboring Regions - a Pha-L Study in the Rat. Journal of Comparative Neurology, 341(3), 289-314.
Antoniadis, E. A., & McDonald, R. J. (2000). Amygdala, hippocampus and discriminative fear conditioning to context. Behavioural Brain Research, 108(1), 1-19.
Balleine, B. W., & Dickinson, A. (1998). Goal-directed instrumental action: Contingency and incentive learning and their cortical substrates. Neuropharmacology, 37(4-5), 407-419.
Barondes, S. H., & Cohen, H. D. (1966). Puromycin effect on successive phases of memory storage. Science, 151(710), 594-595.

延伸閱讀