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

项目摘要 光遗传学是大约10年前发展起来的一种技术，用来对特定类型的 带有光敏蛋白的神经元，因此能够在毫秒内控制这些神经元 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需要病毒转导，这至少需要几个星期的时间 用于表达，并可能在临床应用中引起安全问题。(2)将刚性光纤植入 大脑是侵袭性的，已被证明会产生神经胶质细胞活动和损伤，这对两者都不是可取的。 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输入。该方法将使用碳纳米管作为 一种用于神经元刺激的近红外光吸收器和发热器。因为近红外光可以 这种刺激深入到头骨和脑组织，可以通过使用近红外进行无线刺激 来源在头骨之外。碳纳米管的特定神经元靶向将通过以下方式实现 用抗体或多肽使碳纳米管功能化。 在具体目标1中，我将调整碳纳米管的官能团、浓度和孵化时间 实现低功率近红外光对体外神经元活性的刺激。在具体目标2中，我将申请 多种抗体及其与碳纳米管结合靶向特定细胞的方法 体外受体/通道。在特定的目标3中，我将针对特定的抗体功能化的碳纳米管 近红外光源对小鼠体内神经元受体及体外靶向神经元的刺激作用 头骨。这项拟议工作的结果将是一种无线的、非病毒的方法来刺激特定的 自由活动的动物体内的神经元。

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.