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.

Public Health Relevance

A variety of neuromuscular diseases result in impaired cough (dystussia) and/or impaired swallow (dysphagia). Impairment in these airway protective behaviors results in an increased risk for pulmonary infections due to aspiration of food/liquids. Pulmonary complications related to inadequate airway defense are the leading cause of death in patients with spinal cord injuries, Parkinson's disease, and Alzheimer's disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Career Transition Award (K99)
Project #
5K99HL111215-02
Application #
8626251
Study Section
Special Emphasis Panel (ZHL1-CSR-P (O1))
Program Officer
Tigno, Xenia
Project Start
2013-02-23
Project End
2015-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
2
Fiscal Year
2014
Total Cost
$133,434
Indirect Cost
$9,884
Name
University of Florida
Department
Physiology
Type
Schools of Veterinary Medicine
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Pitts, Teresa; Rose, Melanie J; Poliacek, Ivan et al. (2015) Effect of laparotomy on the swallow-breathing relationship in the cat. Lung 193:129-33
Spearman, Daniel G; Poliacek, Ivan; Rose, Melanie J et al. (2014) Variability of the pharyngeal phase of swallow in the cat. PLoS One 9:e106121
Zubcevic, Jasenka; Santisteban, Monica M; Pitts, Teresa et al. (2014) Functional neural-bone marrow pathways: implications in hypertension and cardiovascular disease. Hypertension 63:e129-39
Silverman, Erin P; Carnaby-Mann, Giselle; Pitts, Teresa et al. (2014) Concordance and discriminatory power of cough measurement devices for individuals with Parkinson disease. Chest 145:1089-96
Pitts, Teresa (2014) Airway protective mechanisms. Lung 192:27-31
Bolser, Donald C; Gestreau, Christian; Morris, Kendall F et al. (2013) Central neural circuits for coordination of swallowing, breathing, and coughing: predictions from computational modeling and simulation. Otolaryngol Clin North Am 46:957-64
Ruddy, Bari Hoffman; Pitts, Teresa E; Lehman, Jeff et al. (2013) Improved voluntary cough immediately following office based vocal fold medialization injections. Laryngoscope :
Pitts, Teresa; Rose, Melanie J; Mortensen, Ashley N et al. (2013) Coordination of cough and swallow: a meta-behavioral response to aspiration. Respir Physiol Neurobiol 189:543-51
Castillo, Daniel; Pitts, Teresa (2013) Influence of baclofen on laryngeal and spinal motor drive during cough in the anesthetized cat. Laryngoscope 123:3088-92