Targeted, wireless neural stimulation with near-infrared light absorbing carbon nanotubes

项目摘要 光遗传学是大约10年前开发的一种技术，用于对特定类型的 神经元与光敏蛋白，从而使这些神经元的控制与光在毫秒 时间分辨率然而，光遗传学有两个主要缺点：（1）光的表达- 特定神经元中的敏感蛋白质需要病毒转导，这至少需要几周的时间 并可能导致临床应用中的安全性问题。(2)刚性光纤植入 脑是侵入性的，并且已经显示出产生神经胶质作用和损伤，这对两者都是不期望的 研究和临床应用。在这里，我将提出一种无线刺激特定神经元的方法， 在不使用病毒和光纤的情况下，该方法将使用碳纳米管作为 用于神经元刺激的近红外光吸收器和热发生器。由于近红外光可以 深入头骨和脑组织，刺激可以通过使用近红外线无线完成。 来源于头骨外碳纳米管对特定神经元的靶向作用将通过以下方式实现： 用抗体或肽官能化碳纳米管。 在特定目标1中，我将调整碳纳米管官能团、浓度和孵育时间， 实现低功率近红外光刺激体外神经元活动。在具体目标2中，我将应用 用于靶向特定细胞的各种抗体和抗体与碳纳米管的缀合方法 体外受体/通道。在具体目标3中，我将靶向抗体功能化的碳纳米管， 神经元受体，并在小鼠体外用近红外光源刺激靶神经元 头骨这项拟议工作的成果将是一种无线的，非病毒的方法，用于刺激特定的 神经元中的一种。

Project Summary Optogenetics is a technique that was developed around 10 years ago to genetically modify specific types of neurons with light-sensitive proteins, and hence enabling the control of these neurons with light in millisecond temporal resolution. However, there are two major disadvantages with optogenetics: (1) Expression of light- sensitive proteins in specific neurons would require virus transduction, which would take at least several weeks for expression and might cause safety issues in clinical applications. (2) Implantation of a rigid optical fiber in the brain is invasive and has been shown to produce glial action and lesions, which are not desirable for both research and clinical applications. Here, I would to propose a method to wirelessly stimulate specific neuron types in without the application of both virus and optical fiber. The approach will be using carbon nanotubes as a near-infrared light absorber and heat generator for neuron stimulation. Since near-infrared light can penetrate deeply in skull and brain tissues, the stimulation can be done wirelessly by using a near-infrared source outside of the skull. The targeting of specific neurons by carbon nanotubes will be achieved by functionalizing carbon nanotubes with antibodies or peptides. In Specific Aim 1, I will tune the carbon nanotube functional groups, concentrations and incubation times to achieve low-power near-infrared light stimulation of neurons activity in vitro. In Specific Aim 2, I will apply various antibodies and antibody conjugation methods with carbon nanotubes for targeting specific cell receptor/channels in vitro. In Specific Aim 3, I will target antibody functionalized carbon nanotubes to specific neurons receptors in vivo and stimulate the targeted neurons with near-infrared light source outside of the mice skull. The outcome of this proposed work will be a wireless, non-viral method for stimulation of specific neurons in a freely behaving animal.