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.

项目摘要 近年来，很明显，调节周围神经系统具有很大的潜力 治疗疾病。为了意识到这一潜力，需要一种新的神经调节方式，该方式是安全的，高度具体的， 并迅速可逆。我们最近表明，将红外神经调节（IRN）应用于周围 诸如Nodose神经节等结构会引起不可能的物理反应的独特模式 通过电流或药物引起。 Nodose神经节在调查许多关键方面起着重要作用 自主功能和IRN应用程序已揭示了一个功能组织 以前尚未描述的神经节。这些结果表明，IRN具有巨大的潜力 绘制神经节中功能响应的拓扑，解码神经节电路和临床 神经心脏装置。 IRN通过诱导短暂时空温度梯度或 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，我们将创建新的设备，以有效，精确地向神经和 动物中的神经节。新设备包括灵活的聚合物波导，可以向多个位置输送光 在与目标组织自由符合和自由移动的同时，一种可以识别的神经节跟踪系统 节点神经节的方向和精确控制神经节上的红外照明模式用于映射 功能和高级钙成像系统，可以对神经节活动进行体积成像和 在活动物中成像。其次，我们将评估IRN的安全性，选择性和可重复性。第三，我们会的 通过进行机械研究，对IRN的工作方式有深刻的了解，包括创建 IRN对电生理学和实验的影响的软化模型，以检验我们的假设。第四， 因为IRN已揭露了一个空间组织来神经节功能，我们将能够映射该组织 详细说明并提供对神经节功能的前所未有的理解。工具和知识获得了 在这笔赠款中，不仅将有助于确定IRN的潜力，而且对未来的神经调节有益 和其他应用。