Interactions of odorants with olfactory receptors and other preprocessing mechanisms: how complex and difficult to predict?

In this issue of Chemical Senses, Münch et al. present a thorough analysis of how mixtures of odorants interact with olfactory receptors (ORs) borne by olfactory receptor neurons (ORNs). Using fruit fly ORNs expressing the receptor OR22a, they provide a clear example of mixture interaction and confirm that the response of an ORN to a binary mixture can be sometimes predicted quantitatively knowing the ORN responses to its components as shown previously in rat ORNs. The prediction is based on a nonlinear model that assumes a classical 2-step activation of the OR and competition of the 2 odorants in the mixture for the same binding site. Can this success be generalized to all odorant-receptor pairs? This would be an encouraging perspective, especially for the fragrance and flavor industries, as it would permit the prediction of all mixtures. To address this question, I outline its conceptual framework and discuss the variety of mixture interactions found so far. In accordance with the effects described in the study of other receptors, several kinds of mixture interactions have been found that are not easily predictable. The relative importance of the predictable and less predictable effects thus appears as a major issue for future developments.