The olfactory mucosa (OM) is the primary site of odorant detection, and its axonal projections relay information to brain structures for signal processing. We have previously observed that olfactory function can be affected during a prolonged stress challenge in Wistar rats. The stress response is a neuroendocrine retro‐controlled loop allowing pleiotropic adaptive tissue alterations, which are partly mediated through the release of glucocorticoid hormones. We hypothesised that, as part of their wide‐ranging pleiotropic effects, glucocorticoids might affect the first step of olfactory detection. To study this, we used a number of approaches ranging from the molecular detection and functional characterisation of glucocorticoid receptors (GRs) in OM cells, to the study of GR acute activation in vivo at the molecular, electrophysiological and behavioural levels. In contrast to previous reports, where GR was reported to be exclusive in olfactory sensory neurones, we located functional GR expression mostly in olfactory ensheathing cells. Dexamethasone (2 mg/kg) was injected intraperitoneally to activate GR in vivo, and this led to functional odorant electrophysiological response (electro‐olfactogram) and OM gene expression changes. In a habituation/cross‐habituation test of olfactory sensitivity, we observed that DEX‐treated rats exhibited higher responsiveness to a complex odorant mixture. These findings support the idea that olfactory perception is altered in stressed animals, as glucocorticoids might enhance odour detection, starting at the first step of detection.

Several factors modulate the first step of odour detection in the rat olfactory mucosa (OM). Among others, vasoactive peptides such as endothelin might play multifaceted roles in the different OM cells. Like their counterparts in the central nervous system, the olfactory sensory neurons are encompassed by different glial-like non-neuronal OM cells; sustentacular cells (SCs) surround their cell bodies, whereas olfactory ensheathing cells (OECs) wrap their axons. Whereas SCs maintain both the structural and ionic integrity of the OM, OECs assure protection, local blood flow control and guiding of olfactory sensory neuron axons toward the olfactory bulb. We previously showed that these non-neuronal OM cells are particularly responsive to endothelin in vitro. Here, we confirmed that the endothelin system is strongly expressed in the OM using in situ hybridization. We then further explored the effects of endothelin on SCs and OECs using electrophysiological recordings and calcium imaging approaches on both in vitro and ex vivo OM preparations. Endothelin induced both robust calcium signals and gap junction uncoupling in both types of cells. This latter effect was mimicked by carbenoxolone, a known gap junction uncoupling agent. However, although endothelin is known for its antiapoptotic effect in the OM, the uncoupling of gap junctions by carbenoxolone was not sufficient to limit the cellular death induced by serum deprivation in OM primary culture. The functional consequence of the endothelin 1-induced reduction of the gap junctional communication between OM non-neuronal cells thus remains to be elucidated.

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