Sensory Pathways of the Oral Cavity and Upper Airways

Abstract

Sensations from the oral cavity convey crucial information about the taste and texture of food. Additionally, oral sensors also respond to temperature changes and various types of noxious substances to alert a organism about potential harm. Similarly, the upper airways contain elaborate sensory systems that steadily monitor airway surfaces for potentially disruptive intruders such as airborne irritants, solid particles, and temperature changes. Airway sensations can evoke powerful responses such as coughing, sneezing, and apnea. The molecular basis of many sensations in the oral cavity and upper airways remains poorly understood. In my dissertation research, I set out to uncover the molecules and cells involved in some of these sensations using genetic tools and functional assays in mice. In my work focusing on the posterior oral cavity, I first set out to address some open questions related to the molecular basis of sour taste sensation. Using whole nerve recordings from the glossopharyngeal nerve, I demonstrate that loss of the ion channel OTOP1 causes major deficit in sour taste responses at the back of the tongue. In contrast, responses to sweet, salty, and bitter taste stimuli remain unaffected. Otop1 knockout mice still have a residual response to sour stimuli, which is completely eliminated with the ablation of taste cells marked by the expression of PKD2L1. Together, current results support OTOP1 ion channel as the main sour sensor, and also reveal an unknown OTOP1-independent pathway through PKD2L1 cells that mediates a component of sour signal in the posterior tongue. In subsequent work looking at downstream sensory neurons, I demonstrate that glossopharyngeal neurons marked by the expression of P2ry1 are essential for conveying sour taste sensation from the posterior tongue to the brain. In addition to taste signaling, I also present my work examining the role of PIEZO2 mechanosensitive channels in the oral cavity. My findings reveal that ablation of glossopharyngeal sensory neurons that express PIEZO2 causes major loss of responses to mechancal force and brushing stimuli in the oral cavity. In another set of experiments, I have explored the molecular basis of water sensation using the larynx as a model system. Application of water in the upper airways, especially the larynx, evokes vigorous physiological responses such as coughing, apnea, and protective swallowing. The incoming water washes away the mucus that normally covers laryngeal surfaces, thus disrupting the extracellular ionic environment. Using whole nerve electrophysiolgical recordings and drinking behavior assays, my experiments demonstrate that removal of extracellular ions serves as a key signaling event to trigger water responses.