Theoretical principles underlying optical stimulation of a channelrhodopsin-2 positive pyramidal neuron
Theoretical principles underlying optical stimulation of a channelrhodopsin-2 positive pyramidal neuron
复制标题
DOI：
10.1152/jn.00501.2011
复制
发表时间：
2012-06-01
影响因子：
2.5
通讯作者：
McIntyre, Cameron C.
中科院分区：
文献类型：
--
作者：
Foutz, Thomas J.;Arlow, Richard L.;McIntyre, Cameron C.
Foutz TJ，Arlow RL，McIntyre CC.视紫红质2通道阳性锥体神经元光学刺激的理论原理。J Neurophysiol 107：3235-3245，2012.首次发表于2012年3月21日; doi：10.1152/jn.00501.2011.-光遗传学是神经调节的新兴领域，其允许使用光对遗传靶向细胞的膜动力学进行缩放的毫秒级时间控制。光遗传学技术已经彻底改变了神经科学的研究，然而，许多生物物理问题仍然存在的光学和神经元的因素影响的调制与光子敏感的离子通道的神经活动。为了开始解决这些问题，我们开发了一种计算工具来探索光遗传学神经刺激的基本原理。这种“光神经元”模型由脑组织中的光纤产生的光动力学的理论表示组成，耦合到嵌入有通道视紫红质-2（ChR 2）膜动力学的皮质锥体神经元的多室电缆模型。模拟显示，产生动作电位所需的大能量主要是由于ChR 2的有限导电性，并且刺激阈值的主要决定因素是照射的细胞膜的表面积和与光源的接近度。我们的研究结果预测，激活阈值是敏感的许多性质的ChR 2（密度，电导率和动力学），组织介质（散射和吸光度），和光纤光源（直径和数值孔径）。我们还说明了重新分布的ChR 2表达密度（均匀与不均匀）的激活阈值的影响。本研究中开发的模型系统代表了表征光遗传神经调节作用的科学工具，以及帮助指导光遗传技术未来发展的工程设计工具。
Foutz TJ, Arlow RL, McIntyre CC. Theoretical principles underlying optical stimulation of a channelrhodopsin-2 positive pyramidal neuron. J Neurophysiol 107: 3235-3245, 2012. First published March 21, 2012; doi: 10.1152/jn.00501.2011.-Optogenetics is an emerging field of neuromodulation that permits scaled, millisecond temporal control of the membrane dynamics of genetically targeted cells using light. Optogenetic technology has revolutionized neuroscience research; however, numerous biophysical questions remain on the optical and neuronal factors impacting the modulation of neural activity with photon-sensitive ion channels. To begin to address such questions, we developed a computational tool to explore the underlying principles of optogenetic neural stimulation. This "light-neuron" model consists of theoretical representations of the light dynamics generated by a fiber optic in brain tissue, coupled to a multicompartment cable model of a cortical pyramidal neuron embedded with channelrhodopsin-2 (ChR2) membrane dynamics. Simulations revealed that the large energies required to generate an action potential are primarily due to the limited conductivity of ChR2, and that the major determinants of stimulation threshold are the surface area of illuminated cell membrane and proximity to the light source. Our results predict that the activation threshold is sensitive to many of the properties of ChR2 (density, conductivity, and kinetics), tissue medium (scattering and absorbance), and the fiber-optic light source (diameter and numerical aperture). We also illustrate the impact of redistributing the ChR2 expression density (uniform vs. nonuniform) on the activation threshold. The model system developed in this study represents a scientific instrument to characterize the effects of optogenetic neuromodulation, as well as an engineering design tool to help guide future development of optogenetic technology.