Regulation of Airway Protective Behaviors

这个项目的长期目标是确定气管和咽感觉反馈的作用

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) Develop a predictive computational distributed network model of the central influence of tracheal sensory pathways on the expression of cough and swallow; and 2) 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. In aim 2, 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; 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.