Infrared Neuromodulation Reveals a New Understanding of Ganglion Organization

红外神经调节揭示了对神经节组织的新认识

• 批准号: 9513867
• 负责人: MICHAEL W. JENKINS
• 金额: $ 277.24万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-06 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9513867
• 关键词: 3-Dimensional; Action Potentials; Adopted; Affect; Animals; Aplysia; Autonomic ganglion; Autonomic nervous system; Autonomic nervous system disorders; Calcium; Cell physiology; Cells; Chronic; Clinical; Collection; Complex; Data; Development; Devices; Diffusion; Digestion; Disease; Electrophysiology (science); Environment; Frequencies; Future; Ganglia; Grant; Heart Rate; Image; Imaging technology; In Vitro; Investigation; Ion Channel; Knowledge; Laboratories; Lasers; Lead; Light; Lighting; Location; Maps; Methods; Microscope; Modality; Modeling; Molecular; Mus; Nerve; Neurons; Nodose Ganglion; Optical Coherence Tomography; Optics; Outcome; Pattern; Peripheral; Peripheral Nervous System; Pharmaceutical Preparations; Pharmacology; Physics; Physiologic pulse; Physiological; Play; Polymers; Positioning Attribute; Preparation; Rattus; Reproducibility; Resolution; Resources; Respiration; Role; Safety; Sampling; Signal Transduction; Site; Space Explorations; Speed; Staining method; Stains; Structure; Surgeon; System; Techniques; Technology; Temperature; Testing; Time; Tissues; Visceral; Width; Work; clinically relevant; design; design and construction; experimental study; flexibility; ganglion cell; genetic manipulation; imaging system; implantation; improved; micromanipulator; miniaturize; neuroregulation; neurotransmission; new technology; novel; optical fiber; patch clamp; pressure; relating to nervous system; response; spatiotemporal; technology development; tool; two-photon

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.

项目概要 近年来，人们已经清楚调节周围神经系统在治疗疾病方面具有巨大潜力。 治疗疾病。为了实现这一潜力，需要一种安全、高度特异性、 并且可快速逆转。我们最近表明，红外神经调节（IRN）应用于外周 诸如结状神经节之类的结构会引起独特的生理反应模式，而这些模式是无法被预测的。 由电流或药物引起。结状神经节在调节许多关键的神经节中发挥着重要作用 自主功能，IRN 应用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结构，解码神经节电路，并作为临床 神经治疗装置。 IRN 通过诱导短暂的时空温度梯度或 通过增加基线温度来抑制活动。我们建议推进 IRN 和成像技术 有以下几种方式。首先，我们将创造新的设备，以高效、精确地将红外光传递到神经和神经系统。 动物的神经节。新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，神经节跟踪系统可以识别目标组织 结状神经节的方向并精确控制神经节上的红外照明模式以进行绘图 功能和先进的钙成像系统，可以对神经节活动进行体积成像 活体动物成像。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 通过进行机械研究（包括创建 IRN 对电生理学影响的复杂模型和实验来检验我们的假设。第四， 因为 IRN 揭示了神经节功能的空间组织，我们将能够绘制该组织的图 详细并提供对神经节功能前所未有的了解。获得的工具和知识 这笔资助不仅有助于确定 IRN 的潜力，而且有利于未来的许多神经调节 和其他应用程序。