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

利用近红外光吸收碳纳米管进行有针对性的无线神经刺激

基本信息

批准号：
9413195
负责人：
Huiliang Wang
金额：
$ 2.47万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-02-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9413195
关键词：
Address Affect Animal Behavior Animals Antibodies Anxiety Autistic Disorder Behavior Brain Brain Diseases Calcium Carbon Nanotubes Cells Charge Clinical Clinical Research Confocal Microscopy Coupled Disadvantaged Dyes Electric Capacitance Electric Stimulation Fiber Fluorescence Goals Heating Image Imagery Implant In Vitro Inflammation Laboratory Study Lasers Lesion Light Mammals Measures Membrane Mental Depression Mental disorders Methods Monitor Movement Mus Neurons Opsin Optics Outcome Parkinson Disease Patch-Clamp Techniques Penetration Peptides Positioning Attribute Proteins Receptor Cell Reporting Research Research Personnel Resolution Safety Source Specificity Surface Techniques Technology Therapeutic Time Tissues Toxic effect Viral Virus Visible Radiation Wait Time Wireless Technology Work absorption antibody conjugate brain tissue cancer cell cancer therapy clinical application clinical translation cranium functional group glial activation implantation in vitro activity in vivo millisecond nervous system disorder neural stimulation optical fiber optogenetics receptor selective expression single walled carbon nanotube success temporal measurement

项目摘要

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.

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。