Most olfactory receptor neurons (ORNs) express a single type of olfactory receptor that is differentially sensitive to a wide variety of odorant molecules. The diversity of possible odorant-receptor interactions raises challenging problems for the coding of complex mixtures of many odorants, which make up the vast majority of real world odors. Pure competition, the simplest kind of interaction, arises when two or more agonists can bind to the main receptor site, which triggers receptor activation, although only one can be bound at a time. Noncompetitive effects may result from various mechanisms, including agonist binding to another site, which modifies the receptor properties at the main binding site. Here, we investigated the electrophysiological responses of rat ORNs in vivo to odorant agonists and their binary mixtures and interpreted them in the framework of a quantitative model of competitive interaction between odorants. We found that this model accounts for all concentration-response curves obtained with single odorants and for about half of those obtained with binary mixtures. In the other half, the shifts of curves along the concentration axis and the changes of maximal responses with respect to model predictions, indicate that noncompetitive interactions occur and can modulate olfactory receptors. We conclude that, because of their high frequency, the noncompetitive interactions play a major role in the neural coding of natural odorant mixtures. This finding implies that the CNS activity caused by mixtures will not be easily analyzed into components, and that mixture responses will be difficult to generalize across concentration.

Molecular biology studies of olfaction have identified a multigene family of molecular receptors that are likely to be involved in odor transduction mechanisms. However, because previous functional data on peripheral coding were mainly collected from inferior vertebrates, it has been difficult to document the degree of specificity of odor interaction mechanisms. As a matter of fact, studies of the functional expression of olfactory receptors have not demonstrated the low or high specificity of olfactory receptors. In this study, the selectivity of olfactory receptor neurons was investigated in the rat at the cellular level under physiological conditions by unitary extracellular recordings. Individual olfactory receptor neurons were broadly responsive to qualitatively distinct odor compounds. We conclude that peripheral coding is based on activated arrays of olfactory receptor cells with overlapping tuning profiles.

Most odours are complex mixtures. However, the capacities of olfactory sensory neurons (OSNs) to process complex odour stimuli have never been explored in air-breathing vertebrates. To face this issue, the present study compares the electrical responses of single OSNs to two odour molecules, delivered singly and mixed together, in rats in vivo. This work is the first aimed at demonstrating that single OSNs simultaneously integrate several chemical signals and which, furthermore, attempts to describe such processes for the whole concentration range over which single OSNs can work. The results stress that complex interactions occur between components in odour mixtures and that OSN responses to such mixtures are not simply predictable from the responses to their components. Three types of interactions are described. They are termed suppression, hypoadditivity and synergy, in accord with psychophysical terminology. This allows us to draw links between peripheral odour reception and central odour coding. Indeed, events occurring in single OSNs may account for the dominating or even the masking effects of odour molecules in complex mixtures, i.e. for the prevailing action of a minor component in the final qualitative perception of a mixture. We conclude that our observations with binary mixtures anticipate the complexity of processes which may rise at the level of a single OSN in physiological conditions. Following this hypothesis, a natural odour would induce a multi-chemical integration at the level of single OSNs which may result in refining their individual odour-coding properties, leading them to play a crucial role in the final performance of the olfactory system.