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.

项目摘要 神经刺激是神经科学中的标准工具，使研究人员可以专门研究个体角色 或神经元组在较大的互连电路中发挥作用。尽管有广泛的适用性，但是 仍然没有可靠的方法来非侵入性刺激特定的神经元集。当前的方法依赖 植入电极，遗传修饰和/或浸润性光纤。这些不仅限制了长期的 这些技术的适用性，但也可能影响测量本身。因此，可靠 非侵入性神经刺激的方法可以推进神经科学领域并启用新的治疗性 神经刺激已显示出希望的疾病的方法。我们已经开发了一种方法 超声能量用于激发压电纳米颗粒。暴露于能量时，压电 纳米颗粒在其表面上积聚电荷。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钙的超声刺激 仅当存在压电纳米颗粒时，才能可靠地发生谷氨酸活性。在这个建议中，我们 寻求在体内应用技术的第一步。该项目的总体目标是确定 压电纳米颗粒可用于实现脑切片中神经元的超声刺激 体内。我们将首先使用大脑识别理想的超声刺激参数和纳米颗粒浓度 切片准备。然后，我们将将这些理想的参数应用于活大鼠。我们将刺激运动皮层 并结合局部场电位和肌电图的组合来测量产生的神经刺激。 总体而言，这项研究将导致表明可以利用压电纳米颗粒以可靠 体内超声神经刺激。