Regulation of Airway Protective Behaviors

描述（由申请人提供）：该项目的长期目标是确定气管和咽感觉反馈在咳嗽和吞咽调节中的作用。我们的中心假设是，一个吸气事件产生一系列咳嗽和吞咽，这些咳嗽和吞咽以各种行为互动模式表达，并且存在可解读的规则来调节各种表达模式。咳嗽和吞咽是气道保护行为。咽咽期通过会厌运动、喉内收、清口和咽防止吸入口腔物质（唾液、食物和液体）。咳嗽是一种吸吸反应行为，可以清除呼吸道中的物质。这些行为的协调对于保护气道免受进一步的吸气促进事件（如咳嗽吸气期发生的吞咽）至关重要。外围输入、操作特征和协调咳嗽和吞咽的主要策略尚不清楚。这种信息的缺乏阻碍了对气道保护缺陷的理解，同时出现吞咽困难和吞咽困难，这与帕金森病和阿尔茨海默病等疾病一起发生。该项目的具体目标是：1)确定在吸入时气管和咽部传入神经激活后控制咳嗽和吞咽运动模式协调的操作原则；2)建立气管感觉通路对咳嗽和吞咽表达中心影响的预测计算分布式网络模型；3)确定网状结构神经元在处理咳嗽和吞咽气管和咽传入反馈中的作用。我们的初步数据证明了咳嗽和吞咽产生的感觉反馈的调节作用。通过吸入刺激刺激气管传入增加吞咽的幅度，提供气道反馈诱导的咽清除率增加的证据。我们观察到一个明显的相位限制关系，当吞咽发生在咽传入反馈咳嗽期间。在第一个目标中，我们将通过同时刺激气管和咽传入的方案来扰乱咳嗽和吞咽运动模式。此外，我们将通过双侧电刺激喉上神经来选择性地控制传入输入。在目标2中，我们将使用网络模拟工具测试气管传入刺激对咳嗽和吞咽协调的中心效应模型，以允许离散的“整合和火”（IF）种群

DESCRIPTION (provided by applicant): The long-term goal of this project is to determine the role of tracheal and pharyngeal sensory feedback in the regulation of cough and swallow. Our central hypothesis is that an aspiration event produces a series of coughs and swallows which are expressed in various behavioral interaction patterns, and that there are decipherable rules that regulate the various patterns of expression. Cough and swallow are airway protective behaviors. The pharyngeal phase of swallow prevents aspiration of oral material (saliva, food and liquid), by epiglottal movement, laryngeal adduction, and clearing the mouth and pharynx. Cough is an aspiration- response behavior that clears material from the airway. Coordination of these behaviors is vital to protect the airway from further aspiration-promoting events, such as a swallow occurring during the inspiratory phase of cough. The peripheral inputs, operational characteristics, and primary strategies that coordinate cough and swallow are unknown. This lack of information impedes understanding of the deficits in airway protection, with co-occurrence of dystussia and dysphagia, which occurs with diseases such as Parkinson's disease and Alzheimer's disease. The Specific Aims of the project are: 1) Identify the operational principles that govern the coordination of cough and swallow motor patterns following activation of tracheal and pharyngeal afferents during an aspiration event; 2) Develop a predictive computational distributed network model of the central influence of tracheal sensory pathways on the expression of cough and swallow; and 3) Identify the role of neurons in the reticular formation in processing tracheal and pharyngeal afferent feedback on cough and swallow. Our preliminary data demonstrates a modulatory effect of sensory feedback of the production of cough and swallow. Stimulation of tracheal afferents by an aspiration stimulus increases the magnitude of swallows, providing evidence of airway feedback-induced increased pharyngeal clearance. We have observed a distinct phase restriction relationship that governs when swallow occurs in response to pharyngeal afferent feedback during cough. In the first aim, we will perturb the cough and swallow motor patterns by protocols that simultaneously stimulate tracheal and pharyngeal afferents. Additionally, we will selectively manipulate afferent input through bilateral electrical stimulation of the superior laryngeal nerve. In aim 2, we will test a model of the central effects of tracheal afferent stimulation on the coordination of cough and swallow using network simulation tools to allow both discrete "integrate and fire" (IF) populations and "hybrid" populations that incorporate Hodgkin-Huxley style equations for sub-threshold currents. In aim 3, we will: 1) record from neurons in the reticular formation using a multi-electrode array to obtain multiple-spike train data during: a) the selective stimulation of the trachea or pharynx to elicit cough or swallow; b) simultaneous stimulation of the trachea and pharynx to elicit coordinated cough and swallow; and c) selective manipulation of cough and swallow using electrical stimulation of the superior laryngeal nerve; 2) test an acute model of dystussia and dysphagia induced by microinjection of the endogenous excitatory amino acid antagonist, kynurenic acid, into the medial reticular formation. The results of these experiments will significantly advance our understanding of the influence of airway and sensory feedback on the coordination of cough and swallow.