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The spatial pattern of light determines the kinetics and modulates backpropagation of optogenetic action potentials

机译：光的空间模式决定动力学并调节光遗传学动作电位的反向传播

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摘要

Optogenetics offers an unprecedented ability to spatially target neuronal stimulations. This study investigated via simulation, for the first time, how the spatial pattern of excitation affects the response of channelrhodopsin-2 (ChR2) expressing neurons. First we described a methodology for modeling ChR2 in the NEURON simulation platform. Then, we compared four most commonly considered illumination strategies (somatic, dendritic, axonal and whole cell) in a paradigmatic model of a cortical layer V pyramidal cell. We show that the spatial pattern of illumination has an important impact on the efficiency of stimulation and the kinetics of the spiking output. Whole cell illumination synchronizes the depolarization of the dendritic tree and the soma and evokes spiking characteristics with a distinct pattern including an increased bursting rate and enhanced back propagation of action potentials (bAPs). This type of illumination is the most efficient as a given irra-diance threshold was achievable with only 6 % of ChR2 density needed in the case of somatic illumination. Targeting only the axon initial segment requires a high ChR2 density to achieve a given threshold irradiance and a prolonged illumination does not yield sustained spiking. We also show that patterned illumination can be used to modulate the bAPs and hence spatially modulate the direction and amplitude of spike time dependent plasticity protocols. We further found the irradiance threshold to increase in proportion to the demyelination level of an axon, suggesting that measurements of the irradiance threshold (for example relative to the soma) could be used to remotely probe a loss of neural myelin sheath, which is a hallmark of several neurodegenerative diseases.
机译：光遗传学提供了前所未有的空间定位神经元刺激的能力。这项研究首次通过仿真研究了激发的空间模式如何影响表达Channelrhodopsin-2（ChR2）的神经元的反应。首先，我们描述了在NEURON仿真平台中对ChR2建模的方法。然后，我们在皮质V层锥体细胞的范例模型中比较了四种最常用的照明策略（体细胞，树突状，轴突和全细胞）。我们表明照明的空间模式对刺激效率和峰值输出的动力学有重要影响。全细胞照明使树突树和体细胞的去极化同步，并以独特的模式唤起尖峰特征，包括增加的爆发率和增强的动作电位（bAP）反向传播。这种类型的照明是最有效的，因为在躯体照明的情况下，仅需要6％的ChR2密度就可以实现给定的红外阈值。仅针对轴突的初始片段需要高的ChR2密度才能达到给定的阈值辐照度，并且长时间的照明不会产生持续的尖峰。我们还表明，图案化照明可用于调制bAP，因此可在空间上调制与峰值时间相关的可塑性协议的方向和幅度。我们进一步发现辐照度阈值与轴突脱髓鞘水平成正比，这表明辐照度阈值（例如相对于躯体）的测量值可用于远程探测神经髓鞘的丢失，这是一个标志。几种神经退行性疾病。

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  • 来源
    《Journal of Computational Neuroscience》 |2013年第3期|477-488|共12页
  • 作者

    Nir Grossman; Vasiliki Simiaki; Claire Martinet; Christofer Toumazou; Simon R. Schultz; Konstantin Nikolic;

  • 作者单位

    Institute of Biomedical Engineering, Department of Electrical and Electronic Engineering, Imperial College London, London SW7 2AZ, UK;

    Department of Bioengineering, Imperial College London, London SW7 2AZ, UK;

    Institute of Biomedical Engineering, Department of Electrical and Electronic Engineering, Imperial College London, London SW7 2AZ, UK;

    Institute of Biomedical Engineering, Department of Electrical and Electronic Engineering, Imperial College London, London SW7 2AZ, UK;

    Department of Bioengineering, Imperial College London, London SW7 2AZ, UK;

    Institute of Biomedical Engineering, Department of Electrical and Electronic Engineering, Imperial College London, London SW7 2AZ, UK;

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  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    Optogenetics; Channelrhodopsin; Neural stimulation;

    机译：光遗传学海豚视紫红质;神经刺激;

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