Neurostimulation by Ultrasound: Physical Biophysical and Neural Mechanisms

项目总结 这个项目的目标是了解超声波效应的神经生物学基础。 (美国)关于神经活动的。US可以在不损伤的情况下改变体外和体内神经元的动作电位活动 神经组织。这一现象可以应用于基础和临床神经科学的强大新工具， 对与精神和神经障碍有关的公共卫生问题产生广泛影响。以指导使用这一新的 工具，我们的研究将提供对物理、生物物理和神经机制的洞察 神经调节。 我们的方法在应用和整合美国神经调节水平的机制研究方面是独一无二的 从单个细胞到整个动物的复杂性。我们的目标是了解 美国1)将声能转化为对生物系统的影响的物理过程以及由此产生的 可测量的物理变量(目标1)，2)生物物理转导过程及其结果 可测量的生物物理效应(目标2)3)导致最终结果的后续神经整合过程 神经系统或行为的输出(目标3)。我们将在三个实验中解决这些问题 模型系统(活体小鼠模型，体外火蜥蜴和小鼠视网膜，以及单个海马区 急性和培养脑片中的锥体细胞)，重点放在我们迄今为止的结果指导的假设上。 美国的神经调节可能会对公共健康产生重大影响。脑刺激疗法是 用于治疗帕金森氏症、肌张力障碍和癫痫，并为许多其他药物带来希望。与.相比 目前的脑刺激技术依赖于侵入性植入电极或空间分辨率有限 和深度穿透(例如经颅磁刺激)，美国提供了空间和空间的理想组合 分辨率、深度穿透性和非侵入性。美国的神经调节也可以在 假体设备；例如，刺激视网膜电路以恢复视力。此外，美国的神经调节 有望成为基础神经科学中非常有用的研究工具，因此它与 所有公共卫生关注的精神和神经障碍。然而，所有这些结果都取决于 能够应用美国的神经调节，获得可控的、可预测的结果。实现这一目标需要一个 我们的多学科研究项目将详细了解美国神经调节的机制 提供。

PROJECT SUMMARY The goal of this project is to understand the neurobiological underpinnings of the effects of ultrasound (US) on neural activity. US can modify action potential activity in neurons in vitro and in vivo without damaging neural tissue. This phenomenon can be applied in powerful new tools for basic and clinical neuroscience, with broad impact on public health issues related to mental and neurological disorders. To guide use of this new tool, our research will provide insight into the physical, biophysical and neural mechanisms underlying US neuromodulation. Our approach is unique in applying and integrating mechanistic studies of US neuromodulation at levels of complexity ranging from the single cell to the whole animal. We aim to understand the relationship between US 1) the physical processes that transform acoustic energy to effects on biological systems and the resulting measurable physical variables (Aim 1), 2) the biophysical transduction processes together with the resulting measurable biophysical effects (Aim 2) 3) the subsequent neural integration processes that lead to the final output of the neural system or behavior (Aim 3). We will address these questions in experiments across three model systems (the in vivo mouse model, in vitro salamander and mouse retina, and single hippocampal pyramidal cells in acute and cultured brain slices), focusing on hypotheses guided by our results thus far. US neuromodulation is likely to have significant impact on public health. Brain stimulation therapies are used to treat Parkinson's disease, dystonia, and epilepsy and hold promise for many others. Compared to current brain stimulation techniques that rely on invasive implanted electrodes or have limited spatial resolution and depth penetration (e.g., transcranial magnetic stimulation), US offers an ideal combination of spatial resolution, depth penetration, and non-invasiveness. US neuromodulation can also be implemented in prosthetic devices; for example, to stimulate retinal circuitry to restore vision. In addition, US neuromodulation promises to become an enormously useful research tool in basic neuroscience, and it is therefore relevant to all mental and neurological disorders of public health concern. However, all these outcomes depend on the ability to apply US neuromodulation with well-controlled, predictable results. Achieving this goal requires a detailed mechanistic understanding of US neuromodulation that our multidisciplinary research project will provide.