Infrared Neuromodulation Reveals a New Understanding of Ganglion Organization

项目摘要 近年来，已经清楚的是，调节周围神经系统具有很大的潜力， 治疗疾病为了实现这一潜力，需要一种新的神经调节方式，它是安全的，高度特异的， 并且快速可逆。我们最近表明，红外神经调制（IRN）时，适用于周边 结构，如结状神经节诱导独特的生理反应模式，不能被 由电流或药物引起的。结状神经节在调节许多关键的神经元活动中起着重要的作用。 自治功能，IRN应用程序已经揭示了不同子区域的功能组织， 之前没有描述过的神经节这些结果表明，IRN具有巨大的潜力， 映射神经节中功能反应的拓扑结构，解码神经节电路，并作为临床 神经细胞装置IRN通过诱导短暂的时空温度梯度来刺激神经活动， 通过增加基线温度来抑制活性。我们建议推进IRN和成像技术， 以下方式。首先，我们将创造新的设备，以有效和精确地将红外光传递到神经， 动物的神经节新的设备包括柔性聚合物波导，可以将光传输到多个位置 在与目标组织一致并自由移动的同时，可以识别目标组织的神经节跟踪系统， 定位结状神经节，并精确控制神经节上的IR照明模式以进行映射 功能，先进的钙成像系统，可以做神经节活动的体积成像， 在活体动物中成像。其次，我们将评估IRN的安全性、选择性和可重复性。三是 通过进行机械研究，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揭示了神经节功能的空间组织，我们将能够映射这种组织 并提供了对神经节功能前所未有的了解。获得的工具和知识 这项资助不仅有助于确定IRN的潜力，而且有利于未来的神经调节 和其他应用。

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.