去抑制機制在果蠅長期記憶固化之角色

A disinhibition mechanism of long-term memory consolidation in Drosophila

馮冠霖(Kuan-Lin Feng)

指導教授 ： 江安世

國立清華大學/生命科學院/生物科技研究所/博士(2021年)

摘要

長期記憶的生成仰賴固化的歷程以克服干擾訊號對記憶的損耗。果蠅的嗅覺記憶透過由投射細胞(projection neuron)傳遞的嗅覺訊號以及由多巴胺神經(dopaminergic neuron)傳遞的電擊訊號匯集至蕈狀體(mushroom body)而生成。然而，訓練後多巴胺的神經活動如何持續地影響記憶的固化歷程依然未知。我們藉由基因操作搭配行為學及電生理來回答這個問題。我們的研究發現: 一、在訓練後，後側腦多巴胺神經(posterior lateral protocerebrum, PPL1)的神經活動會干擾長期記憶的生成。二、神經肽 F (neuropeptide F)會在間格訓練後阻斷來自PPL1-α2α'2和PPL1-α3多巴胺神經的干擾訊號，而允許長期記憶生成。三、我們進一步發現，訓練誘發的神經肽F訊號來自兩顆背前側(dorsal-anterior-lateral)神經DAL2，而從這兩顆神經釋放出的神經肽F及其神經傳導物質是長期記憶生成所必需的。總體來說，我們發現DAL2傳遞神經肽F訊號至特定PPL1多巴胺神經以移除防止長期記憶生成的剎車，藉此機制來確保反覆出現的事件可以被固化成長期記憶。

關鍵字

記憶 ； 固化 ； 神經肽 ； 多巴胺神經

並列摘要

Long-term memory (LTM) formation requires consolidation processes to overcome interfering signals that erode memory formation. Olfactory memory in Drosophila involves convergent projection neuron (PN; odor) and dopaminergic neuron (DAN; reinforcement) input to the mushroom body (MB). How post-training DAN activity in the posterior lateral protocerebrum (PPL1) continues to regulate memory consolidation remains unknown. Here we address this question using targeted transgenes in behavior and electrophysiology experiments to show that (1) persistent post-training activity of PPL1 DANs interferes with aversive LTM formation; (2) neuropeptide F (NPF) signaling blocks this interference in PPL1-α2α'2 and PPL1-α3 DANs after spaced training to enable LTM formation; and (3) training-induced NPF release and neurotransmission from two upstream dorsal-anterior-lateral (DAL2) neurons are required to form LTM. Thus, NPF signals from DAL2 neurons to specific PPL1 DANs disinhibit the memory circuit, ensuring that periodic events are remembered as consolidated LTM.

並列關鍵字

memory ； consolidation ； neuropeptide F ； dopaminergic neurons

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