從哺乳類至果蠅，固化長期記憶皆需要腦中新蛋白質合成來穩固學習引發的突觸改變。
利用黑腹果蠅的嗅覺關聯式學習可以透過氣味與電擊在腦中蕈狀體內的連結來形成多種類型的嗅覺記憶：包含短期、中期與長期記憶。然而，不管是在果蠅還是人類腦中，如何將短期記憶固化為長期記憶一直是個未解但是重要的課題。在本篇研究中，我們利用低溫敏感性的蓖麻毒素阻斷果蠅腦中特定神經細胞的蛋白質新生，藉此策略篩選共一百六十三株，約二十一種蕈狀體輸出神經細胞候選株，鑑定出三種特定類型的蕈狀體輸出神經細胞需要依序生成新蛋白質來固化長期記憶。分別在三種蕈狀體輸出神經中抑制核糖核酸結合ORB蛋白質（哺乳類的CPEB蛋白質異構體）的表現量，皆會影響果蠅的長期記憶。映證此三種蕈狀體輸出神經細胞需要新蛋白質，而新蛋白質的生成受到ORB蛋白質在突觸後的局部轉譯調控。此外，提取果蠅腦中的長期記憶也需要這三種蕈狀體輸出神經細胞的神經傳導物質，說明此三種神經細胞產生新蛋白質進而固化長期記憶，並參與長期記憶提取的神經迴路。綜合以上，本篇研究提出果蠅腦中蕈狀體輸出神經細胞的長期記憶固化模型：ORB蛋白質依序在蕈狀體輸出神經細胞調控突觸後局部新蛋白質生成，藉此將暫時的短期記憶神經活性固化於少數蕈狀體輸出神經細胞的後突觸，最終形成長期記憶。

Creating long-term memory (LTM) requires new protein synthesis to stabilize learning-induced synaptic changes in the brain. In the fruit fly, Drosophila melanogaster, aversive olfactory learning forms several phases of labile memory to associate an odor with coincident punishment in the mushroom body (MB). It remains unclear how the brain consolidates early labile memory into LTM. Here, we survey 163 Gal4 lines containing almost all 21 distinct types of MB output neurons (MBONs) and show that sequential synthesis of learning-induced proteins occurs at three types of MBONs. Downregulation of oo18 RNA-binding proteins (ORBs) in any of these MBONs impaired LTM. And, neurotransmission outputs from these MBONs are all required during LTM retrieval. Together, these results suggest an LTM consolidation model in which transient neural activities of early labile memory in the MB are consolidated into stable LTM at a few postsynaptic MBONs through sequential ORB-regulated local protein synthesis.

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