Optogenetics is revolutionizing Neuroscience, but an often neglected effect of light stimulation of the brain is the generation of heat. In extreme cases, light-generated heat kills neurons, but mild temperature changes alter neuronal function. To date, most in vivo experiments rely on light stimulation of neural tissue using fiber-coupled lasers of various wavelengths. Brain tissue is irradiated with high light power that can be deleterious to neuronal function. Furthermore, absorbed light generates heat that can lead to permanent tissue damage and affect neuronal excitability. Thus, light alone can generate effects in neuronal function that are unrelated to the genuine “optogenetic effect.” In this work, we perform a theoretical analysis to investigate the effects of heat transfer in rodent brain tissue for standard optogenetic protocols. More precisely, we first use the Kubelka-Munk model for light propagation in brain tissue to observe the absorption phenomenon. Then, we model the optothermal effect considering the common laser wavelengths (473 and 593 nm) used in optogenetic experiments approaching the time/space numerical solution of Pennes' bio-heat equation with the Finite Element Method. Finally, we then modeled channelrhodopsin-2 in a single and spontaneous-firing neuron to explore the effect of heat in light stimulated neurons. We found that, at commonly used light intensities, laser radiation considerably increases the temperature in the surrounding tissue. This effect alters action potential size and shape and causes an increase in spontaneous firing frequency in a neuron model. However, the shortening of activation time constants generated by heat in the single firing neuron model produces action potential failures in response to light stimulation. We also found changes in the power spectrum density and a reduction in the time required for synchronization in an interneuron network model of gamma oscillations. Our findings indicate that light stimulation with intensities used in optogenetic experiments may affect neuronal function not only by direct excitation of light sensitive ion channels and/or pumps but also by generating heat. This approach serves as a guide to design optogenetic experiments that minimize the role of tissue heating in the experimental outcome.

中文翻译：

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模拟温度对光遗传学靶向神经元中光刺激的膜响应的影响

光遗传学正在彻底改变神经科学，但光刺激大脑的一个经常被忽视的效应是热量的产生。在极端情况下，光产生的热量会杀死神经元，但温和的温度变化会改变神经元的功能。迄今为止，大多数体内实验依赖于使用各种波长的光纤耦合激光器对神经组织进行光刺激。脑组织被高光功率照射，这可能对神经元功能有害。此外，吸收的光会产生热量，从而导致永久性组织损伤并影响神经元兴奋性。因此，单独的光可以对神经元功能产生影响，而这些影响与真正的“光遗传效应”无关。在这项工作中，我们进行了理论分析，以研究啮齿动物脑组织中传热对标准光遗传学协议的影响。更准确地说，我们首先使用 Kubelka-Munk 模型在脑组织中进行光传播来观察吸​​收现象。然后，我们考虑光遗传学实验中使用的常见激光波长（473 和 593 nm）模拟光热效应，使用有限元方法逼近 Pennes 生物热方程的时间/空间数值解。最后，我们在单个自发发射神经元中模拟了 channelrhodopsin-2，以探索热对光刺激神经元的影响。我们发现，在常用的光强度下，激光辐射会显着增加周围组织的温度。这种效应会改变动作电位的大小和形状，并导致神经元模型中自发放电频率的增加。然而，单次发射神经元模型中由热量产生的激活时间常数的缩短会导致响应光刺激的动作电位失败。我们还发现了伽马振荡的中间神经元网络模型中功率谱密度的变化和同步所需的时间的减少。我们的研究结果表明，光遗传学实验中使用的强度光刺激可能不仅通过光敏离子通道和/或泵的直接激发，而且还通过产生热量来影响神经元功能。这种方法可作为设计光遗传学实验的指南，最大限度地减少组织加热在实验结果中的作用。我们还发现了伽马振荡的中间神经元网络模型中功率谱密度的变化和同步所需的时间的减少。我们的研究结果表明，光遗传学实验中使用的强度光刺激可能不仅通过光敏离子通道和/或泵的直接激发，而且还通过产生热量来影响神经元功能。这种方法可作为设计光遗传学实验的指南，最大限度地减少组织加热在实验结果中的作用。我们还发现了伽马振荡的中间神经元网络模型中功率谱密度的变化和同步所需的时间的减少。我们的研究结果表明，光遗传学实验中使用的强度光刺激可能不仅通过光敏离子通道和/或泵的直接激发，而且还通过产生热量来影响神经元功能。这种方法可作为设计光遗传学实验的指南，最大限度地减少组织加热在实验结果中的作用。