Effects of double and triple bonds on the spatial representations of odorants in the rat olfactory bulb.

Many naturally occurring volatile chemicals that are detected through the sense of smell contain unsaturated (double or triple) carbon-carbon bonds. These bonds can affect odors perceived by humans, yet in a prior study of unsaturated hydrocarbons we found only very minor effects of unsaturated bonds. In the present study, we tested the possibility that unsaturated bonds affect the recognition of oxygen-containing functional groups, because humans perceive odor differences between such molecules. We therefore compared spatial activity patterns across the entire glomerular layer of the rat olfactory bulb evoked by oxygen-containing odorants differing systematically in the presence, position, number, and stereochemistry of unsaturated bonds. We quantified activity patterns by mapping [(14)C]2-deoxyglucose uptake into anatomically standardized data matrices, which we compared statistically. We found that the presence and number of unsaturated bonds consistently affected activity patterns, with the largest effect related to the presence of a triple bond. Effects of bond saturation included a loss of activity in glomeruli strongly activated by the corresponding saturated odorants and/or the presence of activity in areas not stimulated by the corresponding saturated compounds. The position of double bonds also affected patterns of activity, but cis vs. trans configuration had no measurable impact in all five sets of stereoisomers that we studied. These results simultaneously indicate the importance of interactions between carbon-carbon bond types and functional groups in the neural coding of odorant chemical information and highlight the emerging concept that the rat olfactory system is more sensitive to certain types of chemical differences than others.

Differential responses to branched and unsaturated aliphatic hydrocarbons in the rat olfactory system.

In an effort to understand mammalian olfactory processing, we have been describing the responses to systematically different odorants in the glomerular layer of the main olfactory bulb of rats. Previously, we demonstrated chemotopically organized and distinct olfactory responses to a homologous series of straight-chained alkanes that consisted of purely hydrocarbon structures, indicating that hydrocarbon chains could serve as molecular features in the combinatorial coding of odorant information. To better understand the processing of hydrocarbon odorants, we now have examined responses to other types of chemical changes in these kinds of molecules, namely, branching and carbon-carbon bond saturation. To this end, we used the [14C]2-deoxyglucose method to determine glomerular responses to a group of eight-carbon branched alkane isomers, unsaturated octenes (double-bonded), and octynes (triple-bonded). In contrast to the differential responses we observed previously for straight-chained alkanes of differing carbon number, the rat olfactory system was not particularly sensitive to these variations in branching and bond saturation. This result was unexpected, given the distinct molecular conformations and property profiles of the odorants. The similarity in activity patterns was paralleled by a similarity in spontaneous perceptual responses measured using a habituation assay. These results demonstrate again the functional relationship between bulbar activity patterns and odor perception. The results further suggest that the olfactory system does not respond equally to all aspects of odorant chemistry, functioning as a specific, rather than a general, chemical analysis system.

Long hydrocarbon chains serve as unique molecular features recognized by ventral glomeruli of the rat olfactory bulb.

In an effort to understand mammalian olfactory processing, we have been describing the responses to systematically different odorants in the glomerular layer of the main olfactory bulb of rats. To understand the processing of pure hydrocarbon structures in this system, we used the [(14)C]2-deoxyglucose method to determine glomerular responses to a homologous series of alkanes (from six to 16 carbons) that are straight-chained hydrocarbons without functional groups. We found two rostral regions of activity evoked by these odorants, one lateral and one medial, that were observed to shift ventrally with increasing alkane carbon chain length. Furthermore, we successfully predicted that the longest alkanes with carbon chain length greater than our previous odorant selections would stimulate extremely ventral glomerular regions where no activation had been observed with the hundreds of odorants that we had previously studied. Overlaps in response profiles were observed in the patterns evoked by alkanes and by other aliphatic odorants of corresponding carbon chain length despite possessing different oxygen-containing functional groups, which demonstrated that hydrocarbon chains could serve as molecular features in the combinatorial coding of odorant information. We found a close and predictable relationship among the molecular properties of odorants, their induced neural activity, and their perceptual similarities.

Functional mapping of the rat olfactory bulb using diverse odorants reveals modular responses to functional groups and hydrocarbon structural features.

In an effort to understand the olfactory code of rats, we collected more than 1,500,000 measurements of glomerular activity in response to 54 odorants selected to provide differences in functional groups and hydrocarbon structure. Each odorant evoked a unique response pattern by differentially stimulating clusters of glomeruli, called modules. Odorants sharing specific aspects of their structure activated the same modules, allowing us to relate responses to structure across approximately 80% of the glomerular layer. The most obvious relationship was between the presence of particular oxygen-containing functional groups and the activity of glomeruli within dorsal modules. Functional group-specific responses were observed for odorants possessing a wide range of hydrocarbon structure, including aliphatic, cyclic, and aromatic features. Even formic acid and acetone, the simplest odorants possessing acid or ketone functional groups, respectively, stimulated modules specific for these functional groups. At the same time, quantitative analysis of pattern similarities revealed relationships in activation patterns between odorants of similar hydrocarbon structure. The odorant responses were reliable enough to allow us to predict accurately specific aspects of odorant molecular structure from the evoked glomerular activity pattern, as well as predicting the location of glomerular activity evoked by novel odorants.