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研究生： 黃于倫
Hwang, Yu-Luen
論文名稱： 利用衝突訓練模式探討矛盾訊息的記憶形成過程
Investigating the Memory Process of Conflicting Information using Contradictory Training Paradigms
指導教授： 姜學誠
Chiang, Hsueh-Cheng
學位類別： 碩士
Master
系所名稱： 醫學院 - 藥理學研究所
Department of Pharmacology
論文出版年： 2020
畢業學年度： 108
語文別： 英文
論文頁數： 57
中文關鍵詞： 學習記憶 、矛盾記憶 、衝突訓練模式
外文關鍵詞： learning and memory, conflicting memory, contradictory training
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    • 動物的行為模式是大腦經過縝密計算後的總和。然而在日常生活中，有可能因為廣泛的接受到大量訊息而產生矛盾。究竟大腦是如何處理和歸類這些矛盾目前還不得而知。為了理解大腦辨識矛盾的彈性，我們藉由果蠅作為研究的動物模型，利用兩種古典制約模式(嗅覺聯想厭惡及喜好訓練)來進行研究。
    在我們的矛盾的訓練模式下，研究結果顯示相較於單獨使用一種學習的訓練果蠅立即學習表現的能力是較差的。有趣的是，當這些訓練過的果蠅休息了一段時間後，會重新出現了喜好行為。但是與傳統快速形成的抗麻醉性（ARM）記憶與長期記憶（LTM）相比，矛盾訓練下所形成的記憶顯示出明顯的延遲。這暗示了衝突的訊息會破壞正常的記憶形成，尤其穩定型的記憶。另外，透過抑制果蠅蕈狀體（MB）中特定神經元的蛋白質合成，我們也發現此矛盾記憶在果蠅腦中進行接收、固化以及讀取資訊的區域。我們透過人為操縱特定調控厭惡及喜好的多巴胺神經元及蕈狀體輸出的神經元來剖析矛盾記憶的形成過程。我們驚訝的發現矛盾記憶不是傳統的厭惡或喜好的記憶。矛盾記憶會共用厭惡及喜好的部分神經網絡而形成前所未有的全新記憶。

    An animal’s behavior is the result of deliberate and meticulous brain processing. However, on a daily basis, we acquire vast amounts of arbitrary information which can be conflicting. How our brain assorts through this inconsistency is inexplicable. To explore this cognitive flexibility, we consecutively trained the fruit fly, Drosophila melanogaster, under two different olfactory classical conditioning paradigms, aversive and appetitive associative learning; using the same odor for the conditioned stimulus (CS+) in both paradigms.
    Results of our study show that under the contradictory training protocol, flies exhibited poor immediate learning in comparison to learning of either reinforcement used alone. Interestingly, when the same flies were rested after training, over time the approach behavior of appetitive learning then reappears. This appetitive memory formed shows significant and unique delay in its consolidation process, in contrast to the conventional, rapidly consolidated anesthesia-resistant memory (ARM) and appetitive long-term memory (LTM). This suggests that conflicting information results in the disruption of normal memory formation, particularly outstanding in stable form memory. We also uncovered the region of where such conflicting memory is acquired, consolidated and retrieved through the inhibition of protein-synthesis in particular mushroom body (MB) neuron subsets. Through artificial manipulations, we attempted to dissect and partition the components of conflicting memory using specifically designated aversive and appetitive modulating DANs and MBONs. This resulted in a striking revelation of conflicting memory being neither canonical aversive memory nor appetitive memory. Conflicting memory shares neural substrates from both aversive and appetitive memory to give outcome to a whole new unprecedented memory.

    中文摘要 III Abstract V Abbreviations VII Contents VIIIII List of figures X Introduction 1 1.1 Behavior through Learning and Memory 2 1.2 The Drosophila Model 3 1.3 Aversive and Appetitive memory in Drosophila 5 Materials and Methods 7 2.1 Fly strains 8 2.2 Behavioral analyses 8 2.3 Drug feeding 9 2.4 Statistical analysis 9 Results 11 3.1 Contradicotry Training interferes with Initial learning 12 3.2 Conflicting information causes Interference within a 30-minute time window 12 3.3 Appetitive Memory Predominates over time 13 3.4 Contradictory Training disrupts 3-hour Appetitive ARM 13 3.5 Eliminiation of possible Contributing Factors: Pre-exposure of CS+ and Pre-electric shock 15 3.6 Consolidation of Stable memory is Delayed by Contradictory training 15 3.7 Protein synthesis is required in the γ neurons for Consolidation of Long-term Conflicting memory 16 3.8 Acceleration of Conflicting LTM formation via activation of MB γ lobe 17 3.9 MB αβ and α'β' neurons are critical for Conflicting Memory Retrieval 18 3.10 MB γ neurons are critical for Conflicting Memory Acquisition 19 3.11 Inhibition of MB α'β' neurons do not obstruct Conflicting memory Consolidation 19 3.12 Negatively reinforcing Dopaminergic neurons drive Protein synthesis dependent Long-term Conflicting memory 20 3.13 MBON-γ2α'1 is essential for Appetitive memory but not Conflicting memory 20 Discussion and Conclusion 22 4.1 Conclusion 23 4.2 Effect of Conflicting learned information on Memory 23 4.3 Appetitive Phenotypic Conflicting Memory 25 4.4 Memory process of Conflicting Memory 26 4.5 Integration of Approach and Aversion Pathways 28 References 31 Figures 41 Tables 56

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