終紋床核及其腹側海馬下腳輸入參與恐懼記憶形成

Abstract

本論文使用抑制型逃避作業與情境恐懼制約作業探討腹側海馬下腳能否透過它傳送到終紋床核內的麩胺酸神經與終紋床核內正腎上腺素神經互動來影響記憶的形成。研究採用中樞藥物操弄以及電生理記錄，探討在恐懼學習作業學習後相關神經活動的角色。中樞藥物注射的實驗結果顯示，在抑制型逃避作業與情境恐懼制約作業上，刺激腹側海馬下腳內乙醯膽鹼muscarinic受體可調節記憶穩固歷程；在終紋床核內操弄正腎上腺素beta受體以及麩胺酸NMDA受體具有同樣的效果。鑑於操弄腹側海馬下腳影響記憶的效果可以被改變終紋床核內NMDA或beta受體功能壓制，顯示腹側海馬下腳對記憶的作用須透過其投射於終紋床核內之神經進行。上述操弄給在記憶測試前則沒有明顯效果。電生理記錄結果指出，在學習後2至4小時內，終紋床核的神經活動與記憶穩固有關：每隻動物神經活動降低的細胞比率越高，其後的記憶表現越好。這些細胞在學習後第一個小時內的活動較訓練前基準值越低，其後的記憶表現越好，而這樣的關係於學習的第二個小時以後就不明顯。在提取抑制型逃避記憶時，雖然抑制型細胞的比率較多，且終紋床核整體的活動也隨時間增加，但因這個區域並非提取記憶所必要，故此活動可能來自其他更關鍵腦區的影響。於學習後注射損害記憶的scopolamine至腹側海馬下腳會影響到終紋床核的細胞活動的反應形式以及活動出現的時程。學習後注射促進記憶的oxotremorine至腹側海馬下腳並未觀察到神經活動形式上有顯著性的變化，原因可能是電擊參數與前兩個電生理實驗不同所導致。綜合中樞藥物操弄與電生理記錄的結果，腹側海馬下腳確實是透過調節終紋床核的作用而參與記憶穩固歷程，但它們均不涉及記憶的提取；故這兩個結構可能是形成而非儲存記憶神經回路一部份。

This thesis addressed a issue of whether activating the glutamatergic fibers from the ventral subiculum (vSUB) to the bed nucleus of the stria terminalis (BNST) may affect formation and retrieval of fear memory through activating noradrenergic fibers innervating the BNST. The issue was examined by pharmacological manipulation and unit recording in behaving rats. Male Wistar rats were trained on an inhibitory avoidance or contextual fear conditioning task and immediate after training received drug infusion into the vSUB or BNST via indwelling cannulae. Results indicated that posttraining intra-vSUB infusion of scopolamine or oxotremorine impaired or enhanced retention in both tasks, while various drugs infused in the vSUB or BNST shortly before a memory test did not affect retention. Moreover, in each task memory effects of cholinergic manipulation of the vSUB were blocked by altering the BNST glutamatergic or noradrenergic functions. Thus, the vSUB and BNST interacted to affect formation of fear memory, presumably the classical conditioning component. The single unit recording data indicated that rats with more responsive units altering their activity after learning had better retention performance in subsequent retention tests. Moreover, the deactivated response in the first, but not 2nd to 4th hours, after training significantly correlated with subsequent retention, suggesting that the BNST unit deactivation after learning may be critical for memory formation. Posttraining intra-vSUB infusion of a memory-impairing dose of scopolamine altered the BNST neuronal activity by changing the activity patterns and delaying the time of activity change. Posttraining intra-vSUB infusion of a memory enhancing dose of oxotremorine did not induce significant changes of BNST unit activity that well correlated with behavior. In conclusion, our results revealed that the vSUB was involved in memory consolidation processing through interacting with the BNST.