動物對外在環境的感知，及其所產生的反應行為，皆受到大腦神經網路的調控，故若要瞭解動物如何實現複雜行為，需瞭解大腦神經網絡如何形成功能。大腦功能乃根植於神經網絡各組成部分間的聯繫與交互作用，而如何觀察並分析每一腦區所產生的功能性訊號，可說是破譯大腦功能形成機制的關鍵。倘若欲探究大腦功能形成之機制，分析由數百乃至數千的神經細胞所構成的微網絡的介觀動力學將有其必要。著眼於此一挑戰，提出對應之分析演算法，並實際運用於大腦功能形成之探索，就顯得至關重要。為此，本實驗室近幾年已陸續建置一可用於果蠅大腦功能性數據分析之整合性分析平台，功能包含：影像重建及大腦正規化與自動化腦功能區劃定。然而，此平台於果蠅功能性數據實際應用之驗證仍付之闕如。因應此一需求，本研究選定果蠅嗅覺迴路作為研究標的，擷取果蠅在受到氣味刺激時蕈狀體的活化反應數據供分析平台驗證，並藉此探究果蠅之嗅覺迴路。我們一共擷取了11組動、靜態雙光子鈣成像，用以對先前提出之演算法進行驗證。從實驗結果可發現，大腦正規化演算法可確實消弭個體果蠅與標準腦模型間的結構差異，而腦功能區劃定演算法亦獲得了預期中的結果，最終於群體分析中所劃定出的共同活化區域佐證了先前大家對果蠅嗅覺迴路的理解。

Understanding how animals implement complex behaviors requires knowledge of the underlying neuronal circuits in the brain. Prior research substantiates the belief that brain functionality involves the mesoscopic dynamics of micro-networks comprised of hundreds or thousands of neurons rather than few neurons, requiring simultaneous measurements of many individual neurons within the network to investigate. Since there is still a huge discrepancy between current connectomics approaches and the ultimate goal of understanding brain functions, the dynamic of neural networks in higher brain centers remains largely unknown. To pave the way toward establishing a whole-brain integrated connectome, a brain functional data analysis framework, including volumetric image reconstruction, brain warping and functional area delineation, was presented in the previous studies, however, its potential to develop a Drosophila functional connectome database has not been explored. In this study, the framework was employed to the fluorescence data taken by a two-photon optical brain imaging system for investigating the functional pathways of the Drosophila olfactory system. The results demonstrate that the brain functional data analysis framework can not only co-register the functional data of Drosophila individuals into a standard stereotaxic space but also delineate the expected brain regions adequately. The group results of functional area delineation were in common with our previous understanding of the Drosophila olfactory system.

摘要
Abstract
致謝
目錄
圖目錄
表目錄
第一章 緒論---------------------------1
1.1 研究背景--------------------------1
1.2 研究動機與文獻回顧----------------2
1.3 論文架構--------------------------4
第二章 功能性數據擷取與分析平台介紹---5
2.1 高速雙光子顯微成像系統------------5
2.2 影像重建演算法--------------------8
2.3 大腦正規化------------------------8
2.4 腦功能區的劃定--------------------14
2.4.1 鈣離子反應函數的模型建置與估算--14
2.4.2 相關性法與廣義線性模型----------16
2.4.3 假設檢定與隨機場理論------------17
第三章 實驗設計-----------------------20
3.1 原位標準腦模型與標準蕈狀體模型----20
3.2 活體樣品準備----------------------22
3.3 實驗規劃--------------------------24
3.4 常態性試驗------------------------26
第四章 結果與討論---------------------27
4.1 雙光子鈣成像數據重建--------------27
4.2 大腦正規化------------------------29
4.3 動態雙光子鈣成像之數據前處理------40
4.4 腦功能區劃定----------------------41
4.4.1 鈣離子反應函數的估算------------41
4.4.2 假設檢定與隨機場理論------------43
4.4.3 常態性試驗----------------------47
4.4.4 活體果蠅之實驗數據篩選----------50
4.5 群體分析--------------------------51
第五章 結論---------------------------55
參考文獻------------------------------56

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