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 或者一组神经元在一个更大的相互连接的电路中发挥作用。然而，尽管它被广泛应用，但有 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、基因改造和/或侵入性光纤。这些不仅制约了长期 这些技术的适用性，但也可能影响测量本身。因此，一个可靠的 无创神经刺激方法可以推动神经科学领域的发展，使新的治疗方法成为可能 神经刺激已经显示出希望的情况下的方法。我们已经开发出一种方法， 超声波能量被用来激发压电纳米颗粒。当接触到能量时，压电体 纳米粒子在其表面形成电荷。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，超声波刺激钙离子 而谷氨酸活性只有在压电纳米颗粒存在的情况下才能可靠地发生。在这项提案中，我们 寻求迈出在体内应用这项技术的第一步。这个项目的总体目标是建立 这种压电纳米颗粒可以用来对脑片和脑片中的神经元进行超声波刺激 活着。我们将首先利用大脑确定理想的超声刺激参数和纳米颗粒浓度 切片准备。然后，我们将把这些理想的参数应用到活着的老鼠身上。我们会刺激运动皮质 并使用局部场电位和肌电图相结合的方法来测量由此产生的神经刺激。 总而言之，这项研究将证明，压电纳米颗粒可以被用于可靠的 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.