Role and mechanism of transient receptor potential (TRP) channels in gustatory and chemesthetic sensations associated with dietary molecules

"Chemosensory perception", the perception of food chemicals, relies on the complex cooperation of gustatory, olfactory and somatosensory detection systems. In the oral cavity, the taste buds and the lingual branch of the trigeminal nerve are the organs that respond to ingested dietary molecules. Remarkable advances in the understanding of the physiology of these systems have been achieved by identification of key proteins directly implicated in the detection machinery. Among them, several members of the Transient Receptor Potential (TRP) superfamily of ion channels play critical roles in sensory physiology, with contribution in taste, touch, thermosensation and nociception (perception of harmful stimuli). However, even though important key players have been identified, much less is known about their exact role and the specific tuning of their response. In the framework of this Ph.D thesis, I focussed on several dietary molecules possessing complex perceptions and studied their sensory targets. To achieve this, in vitro and in vivo approaches were combined. In a first step, the goal was to answer a simple question: is metallic taste a unique sensation, as are sweet or bitter modalities? To address this issue, the sensory pathways of prototypical metallic tastants being divalent salts of metal cations and artificial sweeteners were evaluated. It was aimed at determining if these molecules could stimulate both somatosensory neurons projecting in the oral cavity and taste buds contained in the papillae. The screening for receptor candidates contained in sensory neurons revealed that these molecules were stimulating TRPV1, the capsaicin (from red hot chilli peppers) receptor. Calcium transients were observed in dissociated sensory neurons from the Dorsal Root Ganglia (DRG) expressing TRPV1 and by using calcium and voltage imaging techniques, a selective stimulation when heterologously expressed in HEK 293 cells was also showed. To elucidate the pathways involved in the perception of sweeteners and metal cations, taste preference assays were performed using mice lacking TRPV1 and TRPM5, the latter being a key channel involved in downstream signalling of sweet, umami and bitter tastes. The results revealed that preference profiles were modified when these two channels were lacking. Direct stimulation of TRPM5 with metallic stimuli did not result in channel opening consistent with a downstream role of this channel in taste cells after activation of the taste GPCR. Remarkably, it was observed that wild type mice displayed strong preference for two metallic stimuli, FeSO4 and ZnSO4 and this preference was absent in mice lacking TRPM5. It was further showed that suppression of T1R3, the receptor of sweet and umami stimuli in taste cells also leads to indifference in the mice, suggesting that these metals induce pleasantness possibly through one of these pathways. Collectively, these data showed that artificial sweeteners and divalent salts elicit biphasic r