Single olfactory sensory neurons simultaneously integrate the components of an odour mixture.

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.

Relation between stimulus and response in frog olfactory receptor neurons in vivo.

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.