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.

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The spiking activity of receptor neurons was recorded extracellularly in the frog olfactory epithelium in response to four odourants applied at precisely controlled concentrations. A set of criteria was formulated to define the spikes in the response. Four variables - latency, duration, number of interspike intervals and frequency - were determined to quantify the responses. They were studied at the single neuron, neuron population and ciliary membrane levels. The dose-response curves were determined using specific functions and their characteristics were evaluated. The characteristic molar concentrations at threshold or at maximum duration and the characteristics of variables, e.g. minimum latency or maximum frequency, have asymmetric histograms with peaks close to the origin and long tails. Dynamic ranges have even more asymmetric histograms, so that a significant fraction of neurons presents a much wider range than their one-decade peak. From these histograms, response properties of the whole neuron population can be inferred. In general, location along the concentration axis (thresholds), width (dynamic ranges) and heights of dose-response curves are independent, which explains the diversity of curves, prevents their global categorization and supports the qualitative coding of odourants. No evidence for odourant-independent types of neurons was found. Finally, receptor activation and ciliary membrane conductance were reconstructed in the framework of a model based on firing data, known mucus biochemical and neuron morpho-electrical characteristics. It is in agreement with independent determinations of Kd of odourant-receptor interaction and of conductance characteristics, and describes their statistical distributions in the neuron population.