外周神经光遗传刺激的计算模型

Nicholas Fritz, Daniel W. Gulick, Jennifer Blain Christen
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引用次数: 1

摘要

刺激一直是研究神经系统潜在机制的关键技术。几十年来,电刺激一直是引起所需肌肉反应的主要方法,但方法仍然是侵入性的,并且对受刺激组织的选择性较低。目前的注射会影响所有的局部组织类型,并可能导致破坏性的免疫反应,威胁神经和设备。光遗传学通过增加特异性和降低对组织的风险,为这种刺激困难提供了解决方案。通过基因修饰,视蛋白(光敏蛋白)被添加到神经元中,并且可以被光激活以引起神经元兴奋。通过在表达通道视紫红质(ChR2)的转基因小鼠体内的初步实验,我们验证了多束光具有叠加效应,并增加了目标神经支配的肌肉的反应。测量后肢屈曲随光源数量的增加而增加。为了进一步表征这种加性效应,生成了一个蒙特卡罗计算机模型来模拟光子通过神经组织的随机行走。该模型显示,光束可以在神经内聚集,尽管是有限的。当使用准直光时,汇聚在神经内部区域的多束光束不会产生比最外层组织最接近单一光源更高的强度。这个模型可以作为一种工具,通过确定光发射参数来帮助未来的动物研究,特别是当试图有选择地刺激给定神经内部深处的区域时,规定需要光学聚焦光。这种能力将允许周围神经刺激的高空间分辨率,从而更好地控制下游组织的兴奋。
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Computational Model of Optogenetic Stimulation in a Peripheral Nerve
Stimulation has been a key technique for studying underlying mechanisms of the nervous system. Electrical stimulation has been the predominant method for eliciting desired muscle responses for decades, yet methodologies remain invasive and low in selectivity of tissue stimulated. Current injection affects all local tissue types and can lead to damaging immune responses that threaten both nerves and equipment alike. Optogenetics provides a solution for such stimulation difficulties by increasing specificity and decreasing risk to tissue. Via genetic modifications, opsins (light-sensitive proteins) are added to neurons, and can be activated by light to cause neuron excitation. Through preliminary in vivo testing in transgenic mice expressing channelrhodopsin (ChR2) we validate that multiple beams of light have an additive effect and increase the response from muscles innervated by the target nerve. Measuring hindlimb flexion increases with increase in number of light sources present. To further characterize this additive effect, a Monte Carlo computer model was generated to simulate a random-walk of photons passing through nerve tissue. The model shows that light beams can aggregate within the nerve, although are limited. When using collimated light, multiple beams converging on the interior region of the nerve cannot result in a higher intensity than outermost layer of tissue nearest a single light source. This model serves as a tool to aid future animal studies by determining light emission parameters, specifically prescribing the need for optically-focused light, when attempting to selectively stimulate regions deep in the interior of a given nerve. Such capability will allow for high spatial resolution of stimulation in peripheral nerves giving finer control of excitation in downstream tissue.
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