Remote Neurostimulation with Ultrasound-activated Piezoelectric Nanoparticles

使用超声波激活压电纳米粒子进行远程神经刺激

• 批准号: 9766304
• 负责人: Geoffrey P. Luke
• 金额: $ 23.15万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9766304
• 关键词: Acoustics; Action Potentials; Antibodies; Area; Axon; Barium; Biological Assay; Brain; Cell Culture Techniques; Cells; Charge; Chronic; Communities; Complex; Culture Media; Data; Development; Disease; Electrodes; Engineering; Equipment; Focused Ultrasound; Gated Ion Channel; Generations; Goals; Heating; Hippocampus (Brain); Implanted Electrodes; Ion Channel Gating; Knowledge; Label; Lasers; Light; Membrane; Methods; Microscopy; Nanotechnology; Neuraxis; Neurologic; Neurons; Neurosciences; Neurosciences Research; Operative Surgical Procedures; Outcome; Penetration; Pharmacology; Physiologic pulse; Property; Prosthesis; Proteins; Rattus; Reporter; Research; Research Priority; Resolution; Resources; Safety; Secondary to; Signal Transduction; Solubility; Specificity; Stimulus; Surface; Techniques; Technology; Testing; Tissues; Transducers; Ultrasonic Therapy; Ultrasonic wave; Ultrasonography; Work; base; behavioral study; biomaterial compatibility; brain volume; cell type; cytotoxicity; fluorescence imaging; genetic manipulation; improved; in vivo; interest; light gated; light scattering; magnetic field; millimeter; nanomaterials; nanoparticle; neural circuit; neural network; neural stimulation; neurofascin; neuropathology; optical imaging; optogenetics; prosthesis control; quasar; receptor; relating to nervous system; response; sensor; spatiotemporal; success; temporal measurement; tool; voltage

Project Summary The ability to trigger neural activity with high resolution millimeters to centimeters deep in tissue remains an elusive goal in neuroscience research. Current research relies on using invasive electrodes, optogenetics, or pharmacological stimulation. None of these technologies, however, is capable of providing large-scale neural stimulation with high spatial resolution. In this project, we propose to combine piezoelectric barium titanate nanoparticles with ultrasound excitation to trigger neural activity. Ultrasound energy can be tightly focused in the brain with very high spatiotemporal resolution. However, ultrasound alone is not an efficient way to activate a specific set of neurons. Thus, we will use barium titanate nanoparticles to act as an embedded transducer to convert ultrasound to electrical energy. We will target the nanoparticles with antibodies to Neurofascin 186 receptors on rat hippocampal membranes, enabling neuron specific labeling at the axon initial segment. Then, highly focused ultrasound energy will be used to depolarize neurons with high spatial specificity. These methods will be validated with optical imaging of cultured rat hippocampal neurons labeled with Quasar, a genetically encoded fluorescent voltage sensor. Finally, we will investigate the mechanisms for action potential generation with the piezoelectric nanoparticles. These results will pave the way for in vivo ultrasound stimulation of groups of neurons at small spatial scales. Overall, the proposed technology has the potential to dramatically improve the ability to study complex neural networks.

项目概要 以高分辨率触发组织深处几毫米到几厘米的神经活动的能力仍然是一个难题 神经科学研究中难以捉摸的目标。目前的研究依赖于使用侵入性电极、光遗传学或 药理刺激。然而，这些技术都无法提供大规模的神经网络 高空间分辨率的刺激。在这个项目中，我们建议结合压电钛酸钡 纳米粒子通过超声波激发来触发神经活动。超声波能量可以紧密聚焦在 大脑具有非常高的时空分辨率。然而，单独使用超声波并不能有效地激活 特定的神经元组。因此，我们将使用钛酸钡纳米粒子作为嵌入式传感器 将超声波转化为电能。我们将用 Neurofascin 186 抗体靶向纳米粒子 大鼠海马膜上的受体，能够在轴突起始段进行神经元特异性标记。然后， 高度聚焦的超声能量将用于以高空间特异性对神经元进行去极化。这些方法 将通过用 Quasar 标记的培养的大鼠海马神经元的光学成像进行验证，Quasar 是一种基因 编码荧光电压传感器。最后，我们将研究动作电位产生的机制 与压电纳米粒子。这些结果将为群体体内超声刺激铺平道路 小空间尺度的神经元。总体而言，所提出的技术有可能显着改善 研究复杂神经网络的能力。