The olfactory epithelium (OE) contains both olfactory sensory neurons (OSNs) and trigeminal fibers, one detecting odorants and the other irritants. However, it is unclear if these two chemosensory systems interact. In trigeminal primary cell cultures, we characterized the calcium responses of trigeminal neurons to odorants with different trigeminal potencies. Using electro-olfactograms (EOGs), we then characterized responses to the same odorants in wild-type (WT) and knockout (KO) mice, which lack the chemosensory trigeminal receptors TRPA1 and TRPV1. The TRPA1 agonists, allyl- isothiocyanate (AITC) and cinnamaldehyde (CNA), showed reduced EOG responses in KO compared to WT mice. No significant differences were observed in response to the odorants pentyl acetate (PA), β-phenyl ethyl alcohol (PEA), both with low trigeminal potency, and the TRPM8 agonist, menthol. Furthermore, brief activations of peptidergic trigeminal fibers by strong trigeminal agonists (AITC and CO 2 ) induced a progressive decrease of OSN responses to a pure olfactory stimulus (PEA). Such modulation is lacking in KO mice and also in the WT when stimulating trigeminal fibers with menthol. Interestingly, when stimulated with CNA or PA, moderate TRPA1 agonists, PEA responses in WT were increased compared to the KO.
We conclude that irritants can modulate EOG responses. We determined that the trigeminal and olfactory systems interact in the OE, with the trigeminal system potentially having a bimodal modulation on olfactory responses. Strong trigeminal irritants cause a reduction of the odor response, while moderate trigeminal agonists might induce an enhancement. The relatively slow (minutes) temporal dynamics of the trigeminal modulation of olfactory responses, and the lack of any modulation by agonists of non- peptidergic fibers (menthol), suggest a mechanism of olfactory modulation mediated by TRPA1/V1 positive trigeminal peptidergic fibers.