Maimon Benjamin E, Zorzos Anthony N, Bendell Rhys, Harding Alexander, Fahmi Mina, Srinivasan Shriya, Calvaresi Peter, Herr Hugh M
MIT Media Lab, Center for Extreme Bionics, Massachusetts Institute of Technology, Cambridge, MA, United States of America. Harvard-MIT program in Health Sciences and Technology (HST), Massachusetts Institute of Technology, Cambridge, MA, United States of America.
J Neural Eng. 2017 Jun;14(3):034002. doi: 10.1088/1741-2552/aa5e20. Epub 2017 Feb 3.
A fundamental limitation in both the scientific utility and clinical translation of peripheral nerve optogenetic technologies is the optical inaccessibility of the target nerve due to the significant scattering and absorption of light in biological tissues. To date, illuminating deep nerve targets has required implantable optical sources, including fiber-optic and LED-based systems, both of which have significant drawbacks.
Here we report an alternative approach involving transdermal illumination. Utilizing an intramuscular injection of ultra-high concentration AAV6-hSyn-ChR2-EYFP in rats.
We demonstrate transdermal stimulation of motor nerves at 4.4 mm and 1.9 mm depth with an incident laser power of 160 mW and 10 mW, respectively. Furthermore, we employ this technique to accurately control ankle position by modulating laser power or position on the skin surface.
These results have the potential to enable future scientific optogenetic studies of pathologies implicated in the peripheral nervous system for awake, freely-moving animals, as well as a basis for future clinical studies.
外周神经光遗传学技术在科学应用和临床转化方面的一个基本限制是,由于生物组织对光的显著散射和吸收,目标神经在光学上难以触及。迄今为止,照亮深部神经靶点需要可植入光源,包括基于光纤和发光二极管的系统,而这两种系统都有明显的缺点。
在此,我们报告一种涉及经皮照射的替代方法。利用在大鼠体内肌肉注射超高浓度的腺相关病毒6-人突触蛋白启动子-通道视紫红质2-增强型黄色荧光蛋白。
我们分别以160毫瓦和10毫瓦的入射激光功率,在4.4毫米和1.9毫米深度实现了对运动神经的经皮刺激。此外,我们利用该技术通过调节激光功率或皮肤表面位置来精确控制踝关节位置。
这些结果有可能为未来对清醒、自由活动动物外周神经系统相关病理进行科学光遗传学研究提供可能,也是未来临床研究的基础。