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.

项目摘要 触发高分辨率毫米以几厘米深度触发神经活动的能力仍然是 神经科学研究中难以捉摸的目标。当前的研究依赖于使用侵入性电极，光遗传学或 药理刺激。但是，这些技术都无法提供大规模神经 刺激高空间分辨率。在这个项目中，我们建议将压电电钛酸钡结合起来 具有超声激发的纳米颗粒会引发神经活动。超声能量可以紧密地集中在 大脑具有很高的时空分辨率。但是，仅超声并不是激活A的有效方法 特定的神经元集。因此，我们将使用钛酸钡纳米颗粒充当嵌入的换能器 将超声转换为电能。我们将针对具有神经曲霉抗体的纳米颗粒186 大鼠海马膜上的受体，在轴突初始段处启用神经元特异性标记。然后， 高度聚焦的超声能量将用于使具有高空间特异性的神经元去极化。这些方法 将通过标记为Quasar标记的培养大鼠海马神经元的光学成像（一种遗传学） 编码的荧光电压传感器。最后，我们将研究动作潜力产生的机制 与压电纳米颗粒。这些结果将为体内超声刺激组铺平道路 在小空间尺度上的神经元。总体而言，拟议的技术有可能显着改善 研究复杂的神经网络的能力。