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研究生: 江國揚
Guo-Yang Chaing
論文名稱: 控制單一神經元的發放時間
Controlling the spiking time in single neuron
指導教授: 陳志強
Chi-Keung Chen
黎璧賢
Lai-Pik Yin
口試委員:
學位類別: 碩士
Master
系所名稱: 理學院 - 生物物理研究所
Graduate Institute of Biophysics
論文出版年: 2016
畢業學年度: 104
語文別: 中文
論文頁數: 69
中文關鍵詞: 發放時間
外文關鍵詞: Reliability of Spike Timing
相關次數: 點閱:17下載:0
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  • 在大腦中,神經元可以用發放來傳遞資訊,並可用發放的時間點來增加資訊的含量。然而,至今尚無法完全了解對於神經元精準的發放的機制。過往研究指出,給予神經元一隨時間波動的刺激能使神經元產生相似性高與準確性高的發放模式(firing pattern)。本實驗研究有兩個部分:刺激波動的快慢與發放時間的影響,另一個為使用一額外控制迴路來控制神經元到目標時間時發放。首先,我們使用膜片鉗技術給予不同相關時間(τ)的Gaussian Exponential Correlated Current﹑得到不同快慢的波動來刺激神經元。細胞樣品使用初代皮質細胞培養的神經元細胞,並在9~13DIV之間進行量測。結果顯示在輸入波動的相關時間為2~10ms時,其發放模式有很高的可靠性和時間準確性。我們另外使用斜波實驗探討刺激上升斜率與發放時間之關係,結果顯示發放時間的準確率與上升斜率成正相關。最後控制實驗中,我們使用隨機最佳控制(Stochastic optimal control)的數值方法,結果顯示成功的在真實的神經元中,使發放時間與目標時間差維持在幾個毫秒內(1~5ms)。


    Precise neural firing is important in the transferring of information. However, we still do not fully understand the mechanism that allows neurons to generate a spike within a narrow temporal regime in the order of a few millisecond. To study the spike timing in a neuron, we perform two types of experiment. Firstly, we stimulate the neuron with different temporal correlated stimuli using patch clamp, and analyze the statistics of corresponding firing patterns; secondly, we apply the stochastic optimal control to manipulate the spiking time. Our samples are from the primary cortical culture. Our result indicates that precision of spike timing is optimal when the correlation times of stimuli are from 2 to 10 ms. In the ramp stimuli experiment, the higher slope of ramp stimuli result in higher precision of spike timing. Obviously, the precision of spike timing depends on stimulus transients. In the stochastic optimal control experiment, the spike timing can be controlled within a few millisecond(1~5ms).

    圖錄.............................................v 使用名詞與定義 ..................................vii Chapter 1 緒論 1.1 前言.........................................1 1.2 神經元(Neuron)...............................1 1.2.1 動作電位(Action Potential).................3 1.2.2 發放閾值(Threshold Potential)..............4 1.2.3 膜電導性(Membrane Conductance).............5 1.2.4 靜止電位(Resting Potential)................6 1.3 神經編碼(Neural Coding)......................7 1.4 隨機最佳控制(Stochastic Optimal Control)......8 Chapter 2 研究內容與方法 2.1初代皮質細胞培養(Primary Cortical Culture).....10 2.2 膜片鉗技術(Patch Clamp)......................10 2.2.1 介紹.......................................10 2.2.2 全細胞膜片鉗(Whole-Cell Patch) .............12 2.2.3 系統架設...................................15 2.3 刺激電流 ― Gaussian Exponential Correlated Current(GECC)....................................17 2.4 分析方法 2.4.1可靠性(Reliability),準確性(Precision)和容差(Tolerance)......................................18 2.4.2 Spike-Triggered Average (STA)..............20 2.5 動態膜片鉗(Dynamic clamp) ― 隨機最佳控制.......21 2.5.1 控制迴路....................................25 2.5.2 控制過程....................................25 Chapter 3 結果 3.1 概要......................................28 3.2 神經元在不同相關時間下的反應................29 3.3 STA與斜波刺激.............................32 3.4 發放時間的隨機最佳控制......................35 Chapter 4 總結與討論 4.1 總結......................................40 4.2 發放的精準度與不確定性的閾值之關係..........40 4.3 閾值下的非線性現象―細胞膜電導率.............41 4.5 控制發放時間的成功率.......................42 4.4 可靠性與神經網路的關係.....................42 參考文獻 Appendix A Protocol of Primary Cortical culture..47 A.1 Culture Medium(CM) A.2 Coating Preparation A.3 Dissection Appendix B Recipe................................49 B.1 Intracellular Solution(ICS) B.2 Balanced Salt Solution(BSS+) Appendix C Protocol of Stimuli...................50 C.1 Gaussian Exponential Correlated current C.2 Parameter of Pipette Puller Appendix D Solution of Hamilton–Jacobi–Bellman (HJB) equation..........................................53

    [1] Chichilnisky, E. J., and R. S. Kalmar. "Temporal resolution of ensemble visual motion signals in primate retina." The Journal of neuroscience 23.17 (2003): 6681-6689.
    [2] Borst, Alexander, and Frédéric E. Theunissen. "Information theory and neural coding." Nature neuroscience 2.11 (1999): 947-957.
    [3] Mainen, Zachary F., and Terrence J. Sejnowski. "Reliability of spike timing in neocortical neurons." Science 268.5216 (1995): 1503-1506.
    [4] Iolov, Alexandre, Susanne Ditlevsen, and André Longtin. "Stochastic optimal control of single neuron spike trains." Journal of neural engineering 11.4 (2014): 046004.
    [5] Verveen, A. A. "On the fluctuation of threshold of the nerve fibre." Structure and function of the cerebral cortex (1960): 282-288.
    [6] Verveen, A. A., and H. E. Derksen. "Fluctuation phenomena in nerve membrane." Proceedings of the IEEE 56.6 (1968): 906-916.
    [7] Pozzorini, Christian, et al. "Temporal whitening by power-law adaptation in neocortical neurons." Nature neuroscience 16.7 (2013): 942-948.
    [8] Stuehmer, Walter, et al. "Structural parts involved in activation and inactivation of the sodium channel." Nature 339.6226 (1989): 597-603.
    [9] Parri, H. Rheinallt, and Vincenzo Crunelli. "Sodium current in rat and cat thalamocortical neurons: role of a non-inactivating component in tonic and burst firing." The Journal of neuroscience 18.3 (1998): 854-867.
    [10] Adrian, Edgar Douglas. "The impulses produced by sensory nerve endings. "The Journal of physiology 61.1 (1926): 49-72.
    [11] Fuglevand, ANDREW J., DAVID A. Winter, and AFTAB E. Patla. "Models of recruitment and rate coding organization in motor-unit pools." Journal of neurophysiology 70.6 (1993): 2470-2488.
    [12] Nabi, Ali, et al. "Minimum energy desynchronizing control for coupled neurons." Journal of computational neuroscience 34.2 (2013): 259-271.
    [13] Hamill, Owen P., et al. "Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches." Pflügers Archiv 391.2 (1981): 85-100.
    [14] Berecki, Géza, et al. "Dynamic clamp as a tool to study the functional effects of individual membrane currents." Patch-Clamp Methods and Protocols (2014): 309-326.
    [15] Destexhe, Alain, et al. "Fluctuating synaptic conductances recreate in vivo-like activity in neocortical neurons." Neuroscience 107.1 (2001): 13-24.
    [16] Aldrich, Richard W., and Charles F. Stevens. "Voltage-dependent gating of single sodium channels from mammalian neuroblastoma cells." The Journal of neuroscience 7.2 (1987): 418-431.
    [17] Scanley, B. E., et al. "Kinetic analysis of single sodium channels from canine cardiac Purkinje cells." The Journal of general physiology 95.3 (1990): 411-437.
    [18] Vandenberg, CAROL A., and R. I. C. H. A. R. D. Horn. "Inactivation viewed through single sodium channels." The Journal of general physiology 84.4 (1984): 535-564.
    [19] White, John A., Jay T. Rubinstein, and Alan R. Kay. "Channel noise in neurons." Trends in neurosciences 23.3 (2000): 131-137.
    [20] Fernandez, Fernando R., Paola Malerba, and John A. White. "Non-linear Membrane Properties in Entorhinal Cortical Stellate Cells Reduce Modulation of Input-Output Responses by Voltage Fluctuations." PLoS Comput Biol 11.4 (2015): e1004188.
    [21] Connors, B. W., M. J. Gutnick, and D. A. Prince. "Electrophysiological properties of neocortical neurons in vitro." Journal of Neurophysiology 48.6 (1982): 1302-1320.
    [22] Ratté, Stéphanie, et al. "Impact of neuronal properties on network coding: roles of spike initiation dynamics and robust synchrony transfer." Neuron78.5 (2013): 758-772.
    [23] Rodriguez-Molina, Victor M., Ad Aertsen, and Detlef H. Heck. "Spike timing and reliability in cortical pyramidal neurons: effects of EPSC kinetics, input synchronization and background noise on spike timing." PloS one 2.3 (2007): e319.
    [24] Berger, Thomas, Matthew E. Larkum, and Hans-R. Lüscher. "High I h channel density in the distal apical dendrite of layer V pyramidal cells increases bidirectional attenuation of EPSPs." Journal of neurophysiology85.2 (2001): 855-868.
    [25] Yamauchi, Satoshi, Hideaki Kim, and Shigeru Shinomoto. "Elemental spiking neuron model for reproducing diverse firing patterns and predicting precise firing times." (2011).
    [26] Mensi, Skander, et al. "Enhanced Sensitivity to Rapid Input Fluctuations by Nonlinear Threshold Dynamics in Neocortical Pyramidal Neurons." PLoS Comput Biol 12.2 (2016): e1004761.

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