MIT Media Lab, Center for Extreme Bionics, Massachusetts Institute of Technology, Cambridge, MA, USA.
Harvard-MIT Program in Health Sciences and Technology (HST), Massachusetts Institute of Technology, Cambridge, MA, USA.
Nat Biomed Eng. 2018 Jul;2(7):485-496. doi: 10.1038/s41551-018-0255-5. Epub 2018 Jun 25.
Technologies for peripheral nerve stimulation have conventionally relied on the anatomic placement of electrodes adjacent to subsets of sensory fibres or motor fibres that selectively target an end effector. Here, we demonstrate the use of optogenetics to directly target the innervating fibres of an end effector by relying on retrograde transfection of adeno-associated virus serotype 6 to restrict axonal opsin expression to the desired fibre targets. By using an in vivo screen in rats, we identify the first channelrhodopsins as well as a halorhodopsin that respond to red light in the peripheral nerve. Combining two channelrhodopsins with spectrally distinct activation profiles allowed us to drive opposing muscle activity via two-colour illumination of the same mixed nerve. We also show halorhodopsin-mediated reductions in electrically evoked muscle tremor spectrally optimized for deep peripheral nerves. Our non-invasive peripheral neurostimulator with targeted multi-fascicle resolution enables scientific and clinical exploration, such as motor control in paralysis, biomimetic sensation feedback for amputees and targeted inhibition of muscle tremor.
传统的周围神经刺激技术依赖于将电极放置在感觉纤维或运动纤维的亚群附近，这些纤维选择性地靶向末端效应器。在这里，我们通过依赖腺相关病毒血清型 6 的逆行转染，将轴突视蛋白表达限制在所需的纤维靶标，从而展示了如何使用光遗传学直接靶向末端效应器的支配纤维。通过在大鼠体内进行筛选，我们确定了第一批对红光有反应的通道视蛋白和一种 halorhodopsin。将两种具有不同光谱激活特性的通道视蛋白结合使用，可以通过对同一混合神经进行双色照射来驱动相反的肌肉活动。我们还展示了 halorhodopsin 介导的肌肉震颤的电诱发减少，其光谱针对深部周围神经进行了优化。我们具有靶向多纤维分辨率的非侵入性周围神经刺激器，可以进行科学和临床探索，例如瘫痪中的运动控制、仿生感觉反馈给截肢者以及肌肉震颤的靶向抑制。
