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A conformational conversion of the cellular prion protein (PrP(C)) is now recognized as the causal event of fatal neurodegenerative disorders, known as prion diseases. In spite of long-lasting efforts, however, the physiological role of PrP(C) remains unclear. It has been reported that PrP(C) is expressed in various areas of the olfactory system, including the olfactory epithelium, but its precise localization in olfactory sensory neurons (OSNs) is still debated. Here, using immunohistochemistry tools, we have reinvestigated the expression and localization of PrP(C) in the olfactory epithelium of adult congenic mice expressing different PrP(C) amounts, that is, wild-type, PrP-knockout, and transgenic PrP(C)-overexpressing animals. We found that PrP(C) was expressed in OSNs, in which, however, it was unevenly distributed, being detectable at low levels in cell bodies, dendrites and apical layer, and more abundantly in axons. We also studied the involvement of PrP(C) in the response of the olfactory epithelium to odorants, by comparing the electro-olfactograms of the 3 mouse lines subjected to different stimulation protocols. We found no significant difference between the 3 PrP genotypes, supporting previous reports that exclude a direct action of PrP(C) in the early signal transduction activity of the olfactory epithelium.

The rodent vomeronasal organ plays an important role in many social behaviors. Using the calcium imaging technique with the dye fluo-4 we measured intracellular calcium concentration changes induced by the application of sulfated steroids to neurons isolated from the vomeronasal organ of female mice. We found that a mix of 10 sulfated steroids from the androgen, estrogen, pregnanolone, and glucocorticoid families induced a calcium response in 71% of neurons. Moreover, 31% of the neurons responded to a mix composed of 3 glucocorticoid-derived compounds, and 28% responded to a mix composed of 3 pregnanolone-derived compounds. Immunohistochemistry showed that neurons responding to sulfated steroids expressed phosphodiesterase 4A, a marker specific for apical neurons expressing V1R receptors. None of the neuron that responded to 1 mix responded also to the other, indicating a specificity of the responses. Some neurons responded to more than 1 individual component of the glucocorticoid-derived mix tested at high concentration, suggesting that these neurons are broadly tuned, although they still displayed strong specificity, remaining unresponsive to high concentrations of the ineffective compounds.