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Abstract

In humans, the perception of volatile substances is multimodal and requires both olfactory and the trigeminal system activation. While olfactory sensory neurons (OSNs) receptive fields are limited to the nasal cavity, trigeminal axons convey sensory information from the head and the neck. Trigeminal neurons are involved in the initiation to protective reflexes and respond to different stimuli modalities such as mechanical pressure, changes in temperature and chemicals, with intensities extending to the noxious range. In contrast, OSNs are mainly activated by odorant chemicals. In the nose, afferents originating from the ophthalmic and maxillary divisions of the trigeminal ganglion, involved in the detection of pungent substances, reside in parallel with olfactory sensory neurons. The proximity of these two systems and psychophysical evidence have led scientists to investigate the possibility of a cross-modality interaction. Most studies have focused on trigeminal modulation of olfactory signals, unravelling a suppressive effect mediated by calcitonine gene-related peptide (CGRP) released from trigeminal afferents. Recently, scientists began to explore the reverse interaction. However, the effect of olfactory stimuli on pungency perception, the possible site of interaction and the molecular pathways underlying it remain unclear. In this thesis, trigeminal innervation was systematically investigated in mice using imaging and electrophysiological techniques to map and characterize anterior ethmoidal nerve afferents within the nasal epithelium. Unexpectedly, during this study, nasal epithelium sections from transgenic reporter mouse line revealed the presence of a subpopulation olfactory sensory neurons expressing the voltage-gated sodium channel NaV 1.8, characteristic for sensory neurons present within dorsal root and trigeminal ganglia. The possibility of a cross-modal interaction between olfactory and trigeminal was interrogated in mice and human. The pure odorant phenylethyl alcohol mitigated irritant aversion to the TRPV1 agonist cyclohexanone and the TRPA1 agonist allyl isothiocyanate diluted in mice. However, these results could not be reproduced in human psychophysical tests. Therefore, the direct influence of OSN activation on trigeminal signalling was assessed using an optogenetic OMP-hChR2Venus mouse line expressing the light-sensitive channel rhodopsin 2 in mature OSNs. Concomitant OSN photo-activation did not affect action potentials signalling in individual trigeminal afferents within the nasal epithelium, suggesting that the mitigating effect observed at behavioural level in mice is unlikely to happen within the nose.