Cellular mechanisms of astringency transduction and sensation - PROJECT SUMMARY Astringency is a dry, puckering flavor sensation that is elicited by phenolic compounds, including tannins, in plant-based foods. The sensation of astringency can drive food choice and potentially impact whether or not we consume healthy, phenol-rich foods. Astringency has long been thought to be a tactile sensation, transduced by oral mechanoreceptors that sense roughness; however, there are gaps in knowledge regarding the mechanisms that underlie phenol transduction and astringent sensation. Multiple models of phenolic compound transduction have been proposed. Some rely on tannin-induced alterations in the biomechanical properties of saliva and the mucosal surface, resulting in enhanced surface roughness, which is then sensed by mechanosensory neurons in the oral mucosa. Other models implicate chemosensory mechanisms of astringency transduction, mediated either by oral mucosal cells that signal to other somatosensory neurons, or direct chemosensory transduction through somatosensory neurons. At this time, there is not a conclusive answer as to whether astringent flavor is chemosensory, mechanosensory, or a combination thereof. Our preliminary data suggest that phenolic compounds are transduced by a trigeminal mechanosensory neuron subpopulation that is tuned to detect movements. This activation occurs in the absence of oral movements, suggesting a chemosensory mode of transduction. Thus, we hypothesize that phenolic compounds directly activate a movement-detecting, tongue- innervating trigeminal mechanosensory neuron subpopulation through chemosensory mechanisms, and that this activation is necessary for astringent perception. In this proposal, we will use a combination of transgenic animals, pharmacology, and molecular methods to define the modes of astringency transduction (e.g., chemosensory or mechanosensory), identify the cellular compartments necessary for transduction and sensation, and determine the molecular signatures of astringent-responsive, tongue-innervating sensory neurons. We will first define the neuronal mechanisms of transduction of astringent compounds (Aim 1) using in vivo and ex vivo functional imaging. Then, we will identify the neuronal and cellular mediators necessary for aversion to astringent compounds using behavioral preference testing (Aim 2). Finally, we will establish the molecular signatures and receptor profiles of tongue-innervating sensory neurons using single cell RNA sequencing and computational analysis (Aim 3). Collectively, these studies will be among the first to systematically test the cellular mechanisms of phenolic compound transduction and sensation, with the long- term goal of understanding the contributions of oral somatosensory neurons to flavor construction.
