Dissemination of a fiber-based optoacoustic neurostimulation device

项目摘要 这是针对家长R01 NS1097914(2018年9月30日至2023年6月30日)的行政补充文件，标题为 通过空间受限刺激和时间分辨记录实现超声神经调节的机制“， 旨在小范围传播一种光纤光声发射器，允许在超高频率下进行超声波神经调节 特殊精确度。父母资助的目的是对细胞和生物物理进行系统分析 超声在亚细胞水平、原代培养神经元和不同脑组织中的作用机制 通过开发新技术，提高清醒小鼠的健康水平。在亲本R01的支持下，PI 他们的同事开发了一种微型光纤光声发射器(FOE)，它可以通过 前所未有的亚毫米空间分辨率。这一技术进步使更深层次的 理解声学刺激的潜在机制。通过将FOE应用于小鼠大脑，直接 声刺激可在不累及耳蜗神经通路的情况下对皮层神经元进行刺激。此外， 通过利用锥形敌人在单个神经元水平上进行刺激，发现兴奋性神经元和 抑制神经元对FOE刺激有不同的反应阈值。两种膜的变形 揭示了相关的快速物理响应和与通道相关的慢响应。建议的传播 旨在将敌人带入广泛的神经系统，包括小鼠皮质、猴子皮质、角膜 神经元和小鼠中央丘脑。基于对新的神经调节技术的需求，我们有 确定了一小部分最终用户。为了交付，我们将把所有的部件组装成一个紧凑型的 便携式光纤光声调制单元。培训将采取两步走的方式。首先，我们将邀请 最终用户实验室的学生/博士后研究员到PI的实验室，以直观地演示我们的 神经调节装置。然后我们将交付完整的系统，并将一名研究生送到最后 用户实验室开展动手培训。考虑到终端用户实验室的不同需求，我们将采取 一个个性化的评估计划，以最大限度地发挥我们设备的潜力。评估将通过以下方式进行 与最终用户的会议，并在培训前、培训后、期中和结束时记录为评估报告 项目期。具体地说，我们的团队将衡量培训前和培训后的技能/知识的置信度 关于资源的使用。最终用户将定量评估技术/资源的优势 而不是其他选择。通过开发替代方法，我们的团队将解决潜在的障碍 在最终用户的实验室中将FOE与录音技术集成时。预计传播这一消息 FOE技术不仅将拓宽对听神经调制机制的理解，而且还将 发起和/或促进与最终用户的长期协作。

Project Summary This administrative supplement for parent R01 NS1097914 (9/30/2018 to 6/30/2023), titled “Unveiling the mechanisms of ultrasound neuromodulation via spatially confined stimulation and temporally resolved recording”, aims at a small dissemination of a fiber optoacoustic emitter that allows ultrasound neuromodulation at ultrahigh special precision. The parental grant aims to perform a systematic analysis of the cellular and biophysical mechanisms of ultrasound stimulation at sub-cellular level, in cultured primary neurons and in different brain regions of awake mice, through development of novel technologies. Under support of the parental R01, the PI and coworkers developed a miniature fiber optoacoustic emitter (FOE) that delivers localized ultrasound with an unprecedented sub-millimeter spatial resolution. This technical advancement has enabled a deeper understanding of the mechanisms underlying acoustic stimulation. By applying FOE to mouse brain, direct acoustic stimulation of cortex neurons without involvement of cochlear pathway was demonstrated. Moreover, by harnessing a tapered FOE for stimulation at single neuron level, it was found that the excitatory neurons and inhibitory neurons have different thresholds in response to FOE stimulation. Both the membrane-deformation related fast physical response and a channel-related slow response are revealed. The proposed dissemination aims to bring FOEs to a broad spectrum of neuronal systems, including mouse cortex, monkey cortex, corneal neurons, and mouse central thalamus. Based on the need for novel neuromodulation technology, we have identified a small cohort of end-users. For delivery, we will assemble all the components into a compact and portable fiber optoacoustic modulation unit. Training will take a two-step approach. First, we will invite students/postdoctoral fellows in the end-users’ lab to the PI’s lab to directly visualize the demonstration of our neuromodulation device. We will then deliver the complete system and send one graduate student to the end users’ lab to carry out a hands-on training. Considering the different needs in end-users’ laboratory, we will take an individualized evaluation plan to maximize the potential of our device. Evaluation will be performed through meetings with end users and documented as evaluation reports at pre-, post-training, mid-term, and end of the project period. Specifically, our team will measure the pre- and post-training confidence level of skills/knowledge regarding use of the resource. The end users will quantitatively evaluate the benefits of the technology/resource over other options. Through development of alternative approaches, our team will address potential hurdles when integrating FOE with the recording technology in end user’s lab. It is expected that dissemination of the FOE technology not only will broaden the understanding of acoustic neuromodulation mechanism, but also will initiate and/or facilitate long-term collaborations with the end users.