蕈狀體-血清素神經迴路對果蠅長期記憶之調控

Serotonin-mushroom body circuit modulating systems consolidation of long-term memory in Drosophila

林萱文(Hsuan-Wen Lin)

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(2015年)

摘要

果蠅經過巴夫洛夫的嗅覺訓練之後，會產生兩種形式的中期記憶：昏迷敏感型記憶 (ASM)，以及抗昏迷型記憶 (ARM)。ASM 的形成和 amnesiac 基因有關，而ARM 的形成則和 radish 基因有關。除了Amnesiac (神經胜肽) 調控ASM外，我們發現，只需要一對 Dorsal Paired Medial (DPM) 神經元釋放血清素到蕈狀體(果蠅嗅覺學習與記憶的中樞)，就可以調控果蠅的中期抗昏迷記憶。
另外，長期記憶的形成，需要多次的學習，使神經訊號的強度超過一個特定的閥值，進而合成新的蛋白質並造成神經突觸的改變。然而，此特定的閥值是如何形成，以及果蠅腦中的記憶神經網絡如何調控此閥值，機制仍不清楚。我們發現，當一次訓練後 (果蠅的學習)，果蠅腦中蕈狀體內的 early alpha/beta KCs 會新合成蛋白質抑制長期記憶的形成；如果抑制 early alpha/beta KC 的蛋白質合成，果蠅只需一次訓練即可形成長期記憶。果蠅的學習會活化 early alpha/beta KCs 內的分子，以及轉錄 5-HT1A；而這些調控果蠅中期抗昏迷記憶的分子，是會抑制蕈狀體下游神經細胞固化長期記憶。這些研究支持果蠅的長期記憶是經由以下機制：在果蠅腦中的三種不同神經元，分別會抑制，增強以及固化果蠅的長期記憶之形成。我們的研究，發現果蠅形成中期記憶以及決定長期記憶是否形成的分子機制，和其所負責調控的神經網絡。

關鍵字

果蠅 ； 蕈狀體 ； 血清素 ； 迴路 ； 長期記憶

並列摘要

Pavlovian olfactory learning in Drosophila produces two genetically distinct forms of intermediate-term memories: anesthesia-sensitive memory, which requires the amnesiac gene, and anesthesia-resistant memory (ARM), which requires the radish gene. In addition to the Amnesiac peptide required for anesthesia-sensitive memory formation, we report that ARM formation requires serotonin (5HT) released from only two dorsal paired medial (DPM) neurons onto the mushroom bodies (MBs), the olfactory learning and memory center in Drosophila. Long-term memory (LTM) formation requires time because information gradually accumulates across widely spaced learning episodes to a threshold that induces protein synthesis and synaptic changes. However, the neural mechanisms that determine this threshold remain obscure. Here, we report that LTM formation from a one-time experience is prevented by induction of new proteins in MB. Blocking protein synthesis in early alpha/beta MB neurons after a single training session induced LTM. Learning was accompanied by activation of molecules in early alpha/beta MB neurons and transcription of the serotonin receptor 5-HT1A, which increased the inhibitory constraints on the storage of LTM in the downstream circuits. We propose that learning induces sequential synthesis of new proteins at three different sites in the brain to inhibit, enhance, and consolidate LTM.

並列關鍵字

Drosophila ； mushroom body ； Serotonin ； circuit ； long-term memory

參考文獻

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