Detection and Characterization of Laryngeal Reflex Pathology in Mouse Models of Human Diseases

Abstract

Objectives: The laryngeal adductor reflex (LAR) is readily triggered in healthy, awake humans by delivering a puff of air to the laryngeal entrance via an endoscope passed through the nose into the throat. LAR impairment has been identified (but not well-characterized) in people with amyotrophic lateral sclerosis (ALS) and is highly correlated with dysphagia. We propose to develop a nonsurgical approach for longitudinal investigation of the LAR in mice. Methods: We designed and constructed an elaborate prototype air pulse delivery system for use with mice. The system interfaces with a miniature endoscope that is small enough for oral insertion into the laryngeal entrance and contains a working channel through which calibrated puffs of air can be delivered, synchronized with rate and phase of the respiratory cycle. Results: We have successfully used this prototype system to evoke and video record (30 fps) the LAR in 10 healthy, C57BL/6 mice under light anesthesia, thus demonstrating proof of concept. Objective quantification of several LAR parameters is currently underway, including total LAR duration, duration of adduction versus abduction phases, and velocity of dorsal angle adduction and abduction. Conclusions: This study provides novel evidence that mice have an LAR similar to humans and that several parameters of the LAR can be objectively quantified in this small animal model. Additional research will include laryngeal brainstem response (LBR) recordings evoked by air pulse triggering of the LAR to elucidate pathological neural substrates in mouse models of ALS and other human diseases that cause dysphagia.