Ultrasound neurostimulation with piezoelectric nanoparticles

压电纳米粒子超声神经刺激

• 批准号: 10312713
• 负责人: Geoffrey P. Luke
• 金额: $ 7.81万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-15 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10312713
• 关键词: 3-Dimensional; Alzheimer' s Disease; Animals; Barium; Brain; Brain region; Calcium; Calcium Signaling; Cell Culture Techniques; Cell surface; Cells; Cerebrospinal Fluid; Charge; Communities; Data; Development; Disease; Electric Stimulation; Electrodes; Electromyography; Emerging Technologies; Environment; Epilepsy; Exposure to; Focused Ultrasound; Funding; Genetic; Glutamates; Goals; Hippocampus (Brain); Implanted Electrodes; In Vitro; Individual; Ion Channel; Label; Lead; Maps; Measurement; Measures; Methods; Modification; Motor; Motor Cortex; Nanotechnology; Neurodegenerative Disorders; Neurons; Neurosciences; Neurosciences Research; Parkinson Disease; Physiologic pulse; Play; Preparation; Rattus; Research; Research Personnel; Risk; Role; Slice; Sprague-Dawley Rats; Stimulus; Surface; Techniques; Technology; Transducers; Ultrasonic Therapy; Ultrasonic Transducer; Ultrasonic wave; Ultrasonics; United States National Institutes of Health; experimental study; extracellular; glutamatergic signaling; in vivo; minimally invasive; nanoparticle; nanoparticle delivery; neural stimulation; neuroregulation; novel therapeutic intervention; optical fiber; pressure; relating to nervous system; response; tool; ultrasound; voltage; voltage gated channel

Project Summary Neural stimulation is a standard tool in neuroscience, allowing researchers to specifically study the role individual or groups of neurons play in a larger interconnected circuit. Despite its widespread applicability, however, there remains no reliable method to noninvasively stimulate a specific set of neurons. Current approaches rely on implanted electrodes, genetic modification, and/or invasive optical fibers. These not only restrict the long-term applicability of these technologies, but also may influence the measurements themselves. Thus, a reliable method for noninvasive neural stimulation could advance the field of neuroscience and enable new therapeutic approaches for conditions where neural stimulation has shown promise. We have developed a method where ultrasound energy is used to excite piezoelectric nanoparticles. Upon exposure to the energy, the piezoelectric nanoparticles build up an electric charge on their surface. We hypothesize that this enables them to trigger voltage sensitive ion channels in the neurons. Our in vitro data indicate that ultrasound stimulation of calcium and glutamate activity only reliably occurs when piezoelectric nanoparticles are present. In this proposal, we seek to take the first steps to applying the technology in vivo. The overall goal of this project is to establish that the piezoelectric nanoparticles can be used to enable ultrasound stimulation of neurons in brain slices and in vivo. We will first identify ideal ultrasound stimulation parameters and nanoparticle concentrations by using brain slice preparations. Then we will apply these ideal parameters to living rats. We will stimulate the motor cortex and use a combination of local field potentials and electromyography to measure the resulting neural stimulation. Overall, this study will result in demonstrating that piezoelectric nanoparticles can be harnessed for reliable ultrasonic neurostimulation in vivo.

项目概要 神经刺激是神经科学中的标准工具，使研究人员能够专门研究个体的作用 或神经元组在更大的互连电路中发挥作用。尽管其应用广泛，但 仍然没有可靠的方法来无创地刺激一组特定的神经元。目前的方法依赖于 植入电极、基因改造和/或侵入性光纤。这些不仅限制了长期 这些技术的适用性，也可能影响测量本身。因此，一个可靠的 非侵入性神经刺激方法可以推动神经科学领域的发展并实现新的治疗方法 神经刺激已显示出希望的条件的方法。我们开发了一种方法，其中 超声波能量用于激发压电纳米颗粒。暴露于能量后，压电 纳米粒子在其表面积聚电荷。我们假设这使他们能够触发 神经元中的电压敏感离子通道。我们的体外数据表明超声刺激钙 谷氨酸活性只有在存在压电纳米颗粒时才会可靠地发生。在这个提案中，我们 寻求在体内应用该技术的第一步。该项目的总体目标是建立 压电纳米颗粒可用于对脑切片和脑组织中的神经元进行超声刺激 体内。我们将首先通过使用大脑确定理想的超声刺激参数和纳米粒子浓度 切片制剂。然后我们将把这些理想的参数应用到活体老鼠身上。我们将刺激运动皮层 并结合局部场电位和肌电图来测量由此产生的神经刺激。 总的来说，这项研究将证明压电纳米粒子可以用于可靠的 体内超声神经刺激。