Central and Peripheral Regulation of Laryngeal Adduction

喉内收的中枢和外周调节

• 批准号: 10642800
• 负责人: DONALD C BOLSER
• 金额: $ 68.61万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-15 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10642800
• 关键词: Aspiration Pneumonia; Behavior; Big Data; Cells; Chemical Stimulation; Clinical; Data; Elderly; Electric Stimulation; Elements; Functional disorder; Goals; Impairment; Ingestion; Interneurons; Investigation; Ipsilateral; Knowledge; Larynx; Lung; Mechanical Stimulation; Mechanics; Mediating; Modeling; Motor; Motor Neurons; Movement; Muscle hypotonia; Neuromechanics; Neurons; Neuropharmacology; Nucleus solitarius; Opioid; Opioid agonist; Organ; Outcome; Pathway interactions; Pattern; Peripheral; Pharmaceutical Preparations; Play; Pneumonia; Production; Reflex action; Regulation; Reticular Formation; Risk; Role; Sensory; Site; System; Techniques; Trachea; adduct; aspirate; data modeling; insight; models and simulation; mortality; neural network; neurogenesis; opioid use; predictive modeling; prevent; protective behavior; resilience; respiratory; response; translational pipeline; vocal cord

PROJECT SUMMARY Opioid use can induce aspiration, which greatly increases the risk of pneumonia. Mortality rates of aspiration pneumonia can approach 40%. The larynx plays a pivotal role in protection of the airways by preventing ingested materials from entering the trachea. This organ participates in different airway protective behaviors, but the initial protective response to intrusion of material is the laryngeal adductor reflex (LAR). The LAR consists of rapid adduction of the vocal folds following stimulation of laryngeal sensory afferents. No information exists on the sensitivity of central pathways responsible for the LAR and their contribution to maladaptive laryngeal responses to opioids. Based on preliminary data and model simulations, we have developed the following hypothesis: opioid-sensitive circuits in the nucleus of the solitary tract and nearby reticular formation (NTS/RF) include a network of neurons with tonic expiratory (t-E) and non- breathing modulated (NBM) activity patterns that regulate reflexive laryngeal adduction through their functional interactions with cells in the ventrolateral respiratory network (VL). This project has two Specific Aims: 1) Identify the network between NTS/RF and VL neurons that regulates the LAR. 2) Determine the central effects of opioids on ipsilateral and crossed pathways in the NTS/RF that regulate coordination of motor drive, mechanics, and vocal fold movements during LAR. We anticipate this project will lead to: a) identification of critical elements of the central reflex pathway for the LAR that are sensitive to opioids, b) identification of the functional relationships for the production and regulation of the LAR: those within NTS inter-neuronal networks, and those between t-E, NBM, NTS/RF, and VL neurons, and c) a new clinically-useful neuromechanical model of vocal fold coordination that will enable prediction of the effects of depressant drugs on the airway protective actions of the larynx. This model will feature functionalities not currently available to clinicians, such as estimation of the impact of unilateral vocal fold hypotonia on laryngeal function. This new knowledge will provide a critical step in understanding the neurogenesis and neuropharmacology of the LAR and how opioids compromise airway protection.

项目概要 使用阿片类药物会引起误吸，从而大大增加患肺炎的风险。误吸死亡率 肺炎可接近40%。喉部在保护气道方面发挥着关键作用，可防止 摄入的物质进入气管。该器官参与不同的气道保护行为， 但对物质侵入的最初保护反应是喉内收肌反射（LAR）。拉尔 包括刺激喉部感觉传入后声带的快速内收。不 存在关于负责 LAR 的中央通路的敏感性及其对 对阿片类药物的喉部适应不良反应。根据初步数据和模型模拟，我们有 提出了以下假设：孤束核中的阿片敏感回路和 附近的网状结构 (NTS/RF) 包括具有强直呼气 (t-E) 和非强直呼气 (t-E) 的神经元网络 呼吸调节（NBM）活动模式，通过其调节反射性喉内收 与腹外侧呼吸网络（VL）中细胞的功能相互作用。这个项目有两个 具体目标： 1) 识别 NTS/RF 和 VL 神经元之间调节 LAR 的网络。 2）确定 阿片类药物对 NTS/RF 中同侧和交叉通路的中心作用，调节协调 LAR 期间的电机驱动、力学和声带运动。我们预计该项目将导致：a) 识别对阿片类药物敏感的 LAR 中枢反射通路的关键元件，b) 确定 LAR 生产和监管的功能关系：NTS 内的功能关系 神经元间网络，以及 t-E、NBM、NTS/RF 和 VL 神经元之间的网络，以及 c) 一种新的临床有用的网络 声带协调的神经力学模型将能够预测抑郁药物的效果 喉部的气道保护作用。该模型将具有目前无法使用的功能 临床医生，如估计单侧声带肌张力低下对喉功能的影响。这个新的 这些知识将为理解 LAR 的神经发生和神经药理学提供关键一步 以及阿片类药物如何损害气道保护。