Ultrasound neurostimulation with piezoelectric nanoparticles

项目摘要 神经刺激是神经科学中的标准工具，允许研究人员专门研究个体的作用。 或者神经元群在一个更大的互联回路中发挥作用。尽管其广泛的适用性，但是， 仍然没有可靠的方法来非侵入性地刺激一组特定的神经元。目前的方法依赖于 植入电极、遗传修饰和/或侵入性光纤。这些不仅限制了长期 这些技术的适用性，但也可能影响测量本身。一个可靠的 一种非侵入性神经刺激的方法可以推进神经科学领域， 神经刺激已经显示出希望的条件的方法。我们开发了一种方法， 超声能量用于激发压电纳米颗粒。在暴露于能量时，压电元件 纳米粒子在其表面上积聚电荷。我们假设这使得它们能够触发 神经元中的电压敏感离子通道。我们的体外实验数据表明，超声刺激钙离子 并且谷氨酸盐活性仅在压电纳米颗粒存在时可靠地发生。在本提案中，我们 寻求迈出将该技术应用于体内的第一步。该项目的总体目标是， 压电纳米颗粒可用于实现脑切片中神经元的超声刺激 vivo.我们将首先确定理想的超声刺激参数和纳米颗粒浓度，通过使用脑 切片制剂。然后我们将这些理想参数应用于活体大鼠。我们会刺激运动皮层 并使用局部场电位和肌电图的组合来测量所产生的神经刺激。 总的来说，这项研究将证明压电纳米颗粒可以用于可靠的 体内超声神经刺激。

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.