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.

项目总结