記憶的形成從早期不穩定的狀態，隨著時間推移並透過新生成的蛋白質，慢慢固
化為得以長期儲存的形式。過去經由對於果蠅嗅覺與電擊之連結學習的研究，建
立了蕈狀體在長期記憶形成過程中所扮演的關鍵角色。然而，蕈狀體數千顆神經
細胞的早期活動，如何固化成需要新生蛋白質之長期記憶的實際過程，至今依舊
是個謎。本研究中，數個獨立的證據顯示，嗅覺長期記憶形成過程中需要兩顆蕈
狀體的輸出神經（MB-V3）；而這兩顆神經也在複雜且廣泛的神經網絡扮演了相
當重要的角色：（１）阻斷MB-V3神經內的蛋白質新生成會對長期記憶造成損害。
（２）在間隔式訓練之後， MB-V3神經會有更高的神經活性；密集式訓練之後則
無。（３）失去嗅覺訊號會導致MB-V3神經與蕈狀體連接的樹突在結構上發生劇
烈的改變。（４）長期記憶的擷取與固化需要來自MB-V3神經的神經傳導。（５）
在MB-V3神經內降低ORB蛋白質的活性會導致長期記憶的缺失；ORB蛋白質參與了
蛋白質轉譯的局部調控。實驗結果暗示了長期記憶的形成包含了一組系統層級的
固化過程。在這個過程中，早期不穩定的嗅覺記憶初步表現在稀疏少數的蕈狀體
神經細胞內，再於MB-V3神經與蕈狀體alpha突出部相接的樹突內，藉由蛋白質新
生成的方式，將不穩定的神經活性轉化為穩定的長期記憶。

Memory is initially labile and gradually consolidated over time through new protein synthesis into a long-lasting stable form. Studies of odor-shock associative learning in Drosophila have established the mushroom body (MB) as a key brain structure involved in olfactory long-term memory (LTM) formation. Exactly how early neural activity encoded in thousands of MB neurons is consolidated into protein-synthesisdependent LTM remains unclear. Here, several independent lines of evidence indicate that changes in two extrinsic MB-output (MB-V3) neurons are required and contribute to an extended neural network involved in olfactory LTM: (i) inhibiting protein synthesis in MB-V3 neurons impairs LTM, (ii) MB-V3 neurons show enhanced neural activity after spaced but not massed training, (iii) MB-V3 dendrites, synapsing with hundreds of MB α/β neurons, exhibit dramatic structural plasticity after removal of olfactory inputs, (iv) neurotransmission from MB-V3 neurons is necessary for LTM retrieval and (v) RNAi-mediated downregulation of oo18 RNA-binding protein (ORB) in MB-V3 neurons impairs LTM. Our results suggest a model of long-term memory formation which includes a systems-level consolidation process, wherein an early, labile olfactory memory represented by neural activity in a sparse subset of MB neurons is converted into a stable LTM through protein synthesis in dendrites of MB-V3 neurons synapsed onto MB α-lobes.

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