指導教授：徐百川、嚴震東臺灣大學：生命科學系吳俊賢Wu, Jose Jiun-ShianJose Jiun-ShianWu2014-11-262018-07-062014-11-262018-07-062014http://ntur.lib.ntu.edu.tw//handle/246246/261688大腦皮質的神經細胞藉由獨特的網路動態活性來進行各種訊息的處理，而神經活性在不同的時空分布下能進行高階的生理功能。近年來有許多的研究專注於探討神經網路運作時所必須具備的特性。已有研究指出負向局部場電位中存在著無尺度以及特定活性事件大小的分布模型（例如：神經雪崩模式），這種神經雪崩模式已在離體神經網路記錄、活體動物實驗記錄（小鼠、大鼠及貓）和人體腦電位記錄中被證實其存在性。不過神經雪崩模式對於大腦皮質的研究仍需要更深入的探討，尤其是對於生理以及病理反應時的分佈變化。本研究中我們假設神經雪崩模式可作為神經網路活性的量測指標。為了證實我們的假設，我們的首要目標是建立起在離體以及活體的神經雪崩模式分析。我們利用了多電極陣列記錄了位於前腦回扣帶皮質以及主要體感覺皮質區這兩個區域的負向局部場電位記錄，並且證實了神經雪崩模式可在我們的紀錄方法中被重現出來。第二部分的實驗我們想了解在不同程度的麻醉下，周邊痛覺刺激對於大腦皮質活性的影響，我們發現了藉由周邊給予痛覺的刺激，在較輕程度的麻醉情形下將會使得神經雪崩模式的分佈斜率改變。在本研究的第三部分中，我們希望在藥物引起的癲癇反應上以及來自丘腦投射所帶給前腦迴扣帶皮質的影響中，比較傳統腦電圖和神經雪崩模式的分析方法，我們發現神經雪崩模式的斜率能和神經網路的興奮性有著顯著的相關。本研究指出神經雪崩模式可作為量測大腦皮質神經網路活性變化的重要指標。Cortical neurons display unique spatiotemporal patterns in signals processing to perform functions. Recent studies focus on the characteristics of the sufficient conditions in neuronal networks. The nLFPs exhibit a scale-free event size distribution, the neuronal avalanche, which has been proven in the cortex across species, including mice, rats, and humans, and may be used as an index of cortical excitability. However, it needs more investigation on the correlation between the neuronal avalanche and the cortical excitabilities. In this study, we hypothesize the neuronal avalanche could be taken as the index of the neuronal network excitability. The first aim of this study is to set up the analysis method of in vitro and in vivo recording. We measured nLFPs from multi-electrode recordings and approved the nLFPs in ACC and the S1 exhibit the distribution of the neuronal avalanche. The second aim of this study is focus on the nociceptive response in different level of the anesthesia, and we found in light anesthesia, the slope of the avalanche, α value, in ACC would be modulated by peripheral nociception. In the third part of this study, we try to evaluate the impact of the network excitability by the medial thalamic manipulation on ACC by traditional EEG analysis and the slope of the neuronal avalanche. We found that the α value could reflect network excitability and the thalamic manipulation. Final we conclude that the neuronal avalanche could be a tool for analyzing cortical network activity in physiological and pathological conditions through nLFPs to determine alterations in network dynamics.致 謝 3 Table of Contents 4 List of the figures 6 List of the tables 7 List of Abbreviation 8 摘要 9 Abstract 10 Introduction 11 The cortical network dynamics: 11 The assessment of the brain functions and the cortical network activities: 11 Neuronal avalanche and the cortical network evaluation: 12 The evaluation of nociception response and the thalamocingulate pathway: 14 Hypothesis of this study and the specific aim: 16 Material and Methods 17 General material and methods: 17 Animals: 17 Acute slice preparation: 17 Animal operation for in vivo recording: 18 Statistical analysis: 18 Method for specific aim (1): Establishment of the neuronal avalanche analysis: 19 Data processing: 19 Neuronal avalanche analysis: 19 Method for specific aim (2): Assessment of the nociceptive modulation in ACC by the neuronal avalanche analysis: 21 Monitoring of the level of the anesthesia: 21 MT lesions: 21 Method for specific aim (3): Assessment of the network excitability in seizure activities in ACC and the impact of the MT inputs: 22 Recording in vitro in seizure induction: 22 Seizure induction in vivo: 22 General analysis of Seizure activities: 23 Branching parameter 24 Results 25 The criteria for the neuronal avalanche assessment in vitro recordings: 25 The evaluation of the neuronal avalanche in vivo recording: 26 Neuronal avalanche is evident in cortical seizure-like activity: 27 Comparison of the neuronal avalanche under nociceptive modulation in the ACC and S1 in light and deep anesthesia: 28 The effect of MT modulation under sensory and nociceptive stimulus in ACC and S1: 28 Neuronal avalanche in an enhanced network activity: 29 Neuronal avalanche in a suppressed network: 31 Cortical network dynamics regulated by medial thalamic inputs: 31 Neuronal avalanche regulated by thalamic inputs in vivo: 33 Neuronal avalanche size and lifetime distribution: 35 Discussion 69 Validation of the neuronal avalanche in in vitro and in vivo recording: 69 Neuronal avalanche and the nociceptive modulation: 69 The anesthesia level and the cortical excitability: 69 Network dynamics in spontaneous cortical activity and neuronal avalanches: 70 Neuronal avalanche in seizure activity: 71 Neuronal avalanche and EEG analysis: 73 Local cortical activity could be modulated by thalamic inputs: 73 Network dynamics and excitation/inhibition balance: 74 Functional application of the neuronal avalanche: 76 Conclusions 77 References 78 Appendix 89 Matlab software code for neuronal avalanche analysis: 895255583 bytesapplication/pdf論文公開時間：2014/03/08論文使用權限：同意有償授權(權利金給回饋學校)神經網路活性神經雪崩模式癲癇痛覺傳遞前扣帶腦迴皮質thesishttp://ntur.lib.ntu.edu.tw/bitstream/246246/261688/1/ntu-103-D95b41009-1.pdf