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.

项目摘要 阿片类药物的使用会导致误吸，从而大大增加患肺炎的风险。吸入死亡率 肺炎可以接近40%。喉在保护呼吸道方面起着关键作用， 摄入的物质进入气管该器官参与不同的气道保护行为， 但对材料侵入的最初保护性反应是喉内收肌反射（LAR）。较大 包括喉感觉传入刺激后声带的快速内收。没有 关于负责LAR的中枢通路的敏感性及其对 对阿片类药物的适应不良的喉部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， 附近的网状结构（NTS/RF）包括紧张性呼气（t-E）和非紧张性呼气（t-E）神经元网络。 呼吸调制（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。该项目有两个 具体目的：1）确定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中调节协调的同侧和交叉通路的中枢作用 电机驱动，力学和声带运动在LAR。我们预计该项目将导致：a） 鉴定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生产和调节的功能关系：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 声带协调的神经力学模型，这将使预测的影响， 喉部的气道保护作用。该模型将具有目前无法提供的功能， 临床医生，如估计单侧声带张力减退对喉功能的影响。这个新 这些知识将为理解LAR的神经发生和神经药理学提供关键的一步 以及阿片类药物如何损害气道保护。