Infrared Neuromodulation Reveals a New Understanding of Ganglion Organization

项目摘要 近年来，人们已经清楚地认识到，调节周围神经系统对 治疗疾病。为了实现这种潜力，需要一种新的神经调节方式，它是安全的，高度特异的， 而且可以迅速逆转。我们最近发现，红外线神经调节(IRN)应用于外周时 像结状神经节这样的结构诱导出独特的生理反应模式，这是不可能的 由电流或药物引起的。结状神经节在调节多种危重疾病中起着重要作用 自主功能，IRN应用程序揭示了不同子区域的功能组织 以前没有描述过的神经节。这些结果表明，IRN具有巨大的潜力 绘制神经节功能反应的拓扑图，解码神经节回路，并作为临床应用 神经治疗仪。IRN通过诱导短暂的时空温度梯度或 通过提高基线温度来抑制活动。我们建议推动IRN和成像技术在 有以下几种方式。首先，我们将创造新的设备，高效而准确地向神经和 动物的神经节。新设备包括可将光传输到多个位置的柔性聚合物波导 在与目标组织相适应和自由移动的同时，神经节跟踪系统可以识别 结状神经节的定位和精确控制神经节上的红外照明模式以进行标测 功能，以及先进的钙成像系统，可以对神经节活动和 在活体动物身上进行成像。其次，我们将评估IRN的安全性、选择性和可重复性。第三，我们将 通过进行机制研究深入了解IRN的工作原理，包括创建 IRN对电生理学影响的复杂模型和实验来验证我们的假设。第四, 由于IRN已经揭开了神经节功能的空间组织，我们将能够绘制出该组织的地图 并对神经节细胞的功能有了前所未有的了解。所获得的工具和知识 这项资助不仅有助于确定IRN的潜力，而且对未来的一系列神经调节有利 和其他应用程序。

Project Summary In recent years, it has been become clear that modulating the peripheral nervous system has great potential for treating diseases. To realize this potential, a new neuromodulation modality is needed that is safe, highly specific, and rapidly reversible. We have recently shown that infrared neuromodulation (IRN) when applied to peripheral structures such as the nodose ganglion induces unique patterns of physiological responses that cannot be elicited by electrical current or drugs. The nodose ganglion plays an important role in regulating many critical autonomic functions, and IRN application has unmasked a functional organization for different sub-regions of the ganglion that has not been previously described. These results suggest that IRN has enormous potential for mapping the topology of functional responses in ganglia, decoding ganglionic circuitry, and as a clinical neuroceutical device. IRN stimulates neural activity by inducing a brief spatiotemporal temperature gradient or inhibits activity by increasing the baseline temperature. We propose to advance IRN and imaging technology in the following ways. First, we will to create new devices to efficiently and precisely deliver IR light to nerves and ganglia in animals. New devices include flexible polymer waveguides that can deliver light to multiple locations while conforming and moving freely with the target tissue, a ganglia tracking system that can identify the orientation of the nodose ganglion and precisely control IR illumination patterns on the ganglia for mapping function, and advanced calcium imaging systems that can do volumetric imaging of ganglionic activity and imaging in living animals. Second, we will assess the safety, selectivity, and repeatability of IRN. Third, we will develop a deep understanding of how IRN works by conducting mechanistic studies that include creating sophisticated models of IRN’s effect on electrophysiology and experiments to test our hypotheses. Fourth, because IRN has unmasked a spatial organization to ganglionic function, we will be able to map this organization in detail and provide an unprecedented understanding of ganglionic function. The tools and knowledge gained in this grant will not only help determine the potential of IRN, but be beneficial to a host of future neuromodulation and other applications.