Central and Peripheral Regulation of Laryngeal Adduction

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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.