School of Biological and Health Systems Engineering, Arizona State University, Tempe, 85282, USA.
Department of Electrical, Computer, and Energy Engineering, Arizona State University, Tempe, 85282, USA.
Sci Rep. 2021 Nov 19;11(1):22588. doi: 10.1038/s41598-021-01353-9.
Optogenetics presents an alternative method for interfacing with the nervous system over the gold-standard of electrical stimulation. While electrical stimulation requires electrodes to be surgically embedded in tissue for in vivo studies, optical stimulation offers a less-invasive approach that may yield more specific, localized stimulation. The advent of optogenetic laboratory animals-whose motor neurons can be activated when illuminated with blue light-enables research into refining optical stimulation of the mammalian nervous system where subsets of nerve fibers within a nerve may be stimulated without embedding any device directly into the nerve itself. However, optical stimulation has a major drawback in that light is readily scattered and absorbed in tissue thereby limiting the depth with which a single emission source can penetrate. We hypothesize that the use of multiple, focused light emissions deployed around the circumference of a nerve can overcome these light-scattering limitations. To understand the physical parameters necessary to produce pinpointed light stimulation within a single nerve, we employed a simplified Monte Carlo simulation to estimate the size of nerves where this technique may be successful, as well as the necessary optical lens design for emitters to be used during future in vivo studies. By modeling multiple focused beams, we find that only fascicles within a nerve diameter less than 1 mm are fully accessible to focused optical stimulation; a minimum of 4 light sources is required to generate a photon intensity at a point in a nerve over the initial contact along its surface. To elicit the same effect in larger nerves, focusing lenses would require a numerical aperture [Formula: see text]. These simulations inform on the design of instrumentation capable of stimulating disparate motor neurons in mouse sciatic nerve to control hindlimb movement.
光遗传学为与神经系统进行交互提供了一种替代方法,优于电刺激这一黄金标准。虽然电刺激需要将电极通过手术嵌入组织中进行体内研究,但光刺激提供了一种侵入性更小的方法,可能产生更特异、更局限的刺激。具有光遗传学特性的实验动物的出现——其运动神经元在受到蓝光照射时可以被激活——使人们能够深入研究对哺乳动物神经系统进行光刺激的方法,其中可以在不将任何装置直接嵌入神经本身的情况下刺激神经内的亚组神经纤维。然而,光刺激有一个主要的缺点,即光很容易在组织中散射和吸收,从而限制了单个发射源可以穿透的深度。我们假设,使用多个聚焦的光发射源,部署在神经的周围,可以克服这些光散射限制。为了了解在单个神经内产生精确光刺激所需的物理参数,我们采用简化的蒙特卡罗模拟来估计这种技术可能成功的神经直径大小,以及在未来的体内研究中使用发射器所需的必要光学透镜设计。通过对多个聚焦光束进行建模,我们发现只有直径小于 1 毫米的神经束内可以完全接受聚焦光刺激;需要至少 4 个光源才能在神经表面的初始接触点上产生在神经内某点的光子强度。为了在更大的神经中产生相同的效果,聚焦透镜将需要数值孔径[公式:见文本]。这些模拟为设计能够刺激小鼠坐骨神经中不同运动神经元以控制后肢运动的仪器提供了信息。