QUALITATIVE AND QUANTITATIVE DISCRIMINATION IN THE FROG OLFACTORY RECEPTORS: ANALYSIS FROM ELECTROPHYSIOLOGICAL DATA

The increasing success of biochemistry in identifying and extracting protein acceptors for various substrates like hormones or neural transmitters is leading more and more physiologists to think that the ultimate mechanism of olfactory tranduction must be some kind of molecular interaction between odorants and macromolecular acceptors, presumably proteins, situated in the apical membrane of the olfactory receptor cells. Testing the occurence and properties of stimulusacceptor complexes hence appears to be an unavoidable bottleneck for a better understanding of olfaction. Two major quantitative limits have delayed a direct biochemical approach: In the first place, the amount of specific material available from olfactory membranes is very small, and, second, odorants are very weakly bound to acceptor sites. The stimulus-acceptor complexes are therefore expected to be generated in such minute quantities that no known labeling technique could help detect them. We are thus reduced to rely on the only available indicator, the physiological response itself, which is ideally sensitive but seriously limited in specificity by its all-or-none nature: once triggered, the firing of an olfactory receptor cell behaves independently of its cause and tells nothing about it. In order to make sense, it becomes necessary to modify the physicochemical environment of sensory cells and try to find physicochemical factors having a predictable influence on the cell responses. A careful analysis of the correlations between external physicochemical conditions and response patterns remains our best chance for an asymptotic appraisal of membrane acceptors. The experiments reported and discussed in this paper have been conducted according to this philosophy. We have first evaluated our indicator, the single olfactory nerve fiber response, on the grounds of sensitivity and reproducibility: we have then set forth the simplest possible question about the olfactory acceptors: How many are they? Because it is well demonstrated that every given olfactory fiber displays its own spectrum of sensitivity, we have not attempted to classify or categorize their response profiles: instead, we have decided to investigate as a whole the set of responses of a large sample of receptor cells to a variety of odors, trying to outline significant odor clusters in a multidimensional olfactory space through responsepattern similarities.