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

We have been describing systematic differences in the spatial activity patterns in the glomerular layer of the rat olfactory bulb that are evoked by odorants that differ systematically in chemical structure (e.g., carbon number, functional group, open versus closed-chain structures, enantiomers, and stereoisomerism involving different branching and functional group position; Johnson et al., 1998, 1999, 2002, 2004, 2005a,b, 2006; Linster et al., 2001; Johnson and Leon 2000a,b; Ho et al., 2006a,b; Farahbod et al., 2006). Individual glomeruli in the bulb appear to receive convergent input from nasal olfactory sensory neurons that express the same single odorant receptor gene, and the location of glomeruli associated with the same odorant receptor are remarkably consistent from animal to animal (Mombaerts et al., 1996). By mapping the responses of glomeruli in the bulb to systematically related odorants, we therefore have been able to identify a number of molecular features that are particularly important in determining the response specificity of particular parts of the glomerular layer and their related receptors (Leon and Johnson, 2003). These responses typically involve glomeruli that are clustered with respect to odorant specificity, and the clusters often contain systematic arrangements of glomeruli that are related to particular chemical properties such as molecular length (Johnson et al., 1998, 1999, 2004; Johnson and Leon, 2000b; Ho et al., 2006a). The resulting overall patterns of activity appear to be relevant to perception in that the degree of similarity in the patterns is predictive of the degree of similarity in perceived odor for a variety of series of closely related odorant chemicals (Linster et al., 2001; Cleland et al., 2002; Schaefer et al., 2002; Ho et al., 2006a,b). As part of a study of systematically differing odorant hydrocarbon structures, we recently included hydrocarbons differing in the presence, number, position, and stereochemistry of double bonds and triple bonds (Ho et al., 2006b), which are functional groups that can participate as acceptors in hydrogen bonding. Replacing a single carbon-carbon bond with a double or triple bond reduces flexibility, decreases hydrophobicity, and results in different shapes compared to the corresponding saturated compounds, all aspects of ligands that we would expect to lead to differences in receptor binding. We therefore were surprised that the presence and characteristics of these bonds did not have very much of an effect on the spatial representations of hydrocarbon odorants (Ho et al., 2006b). The main effects we detected were a decrease in the activation of ventral modules with decreasing bond saturation, especially when the double or triple bonds were present in the middle of the open-chained compounds. Given a similar effect of the presence of methyl substitution in the middle of these same open-chained compounds, the most likely explanation of this phenomenon seemed to be a relatively non-specific disruption of receptor binding to the longest available straight hydrocarbon chain in the odorant molecule (Ho et al., 2006b). However, the presence of double and triple bonds affects the perception of odors of a number of odorants as judged by humans (Table 1; Arctander, 1994; Hatanaka et al., 1992). In some cases, these effects appear to be subtle, such as the differences between 3,7-dimethyloctanol (single bonded) and citronellol (double bonded), whereas the effects appear more dramatic in other cases, such as the difference between fruity and green odor descriptors associated with the single-bonded methyl octanoate and the triple-bonded methyl 2-octynoate (Table 1). Differences in the position, number, and stereochemistry of double bonds also can change minor odor notes or modifying descriptors such as “sweet” or “dry” that are applied by humans (Table 1). Table 1 Double and triple bonds affect odor descriptors that are applied to odorants. Many of the odorants displaying differential odors with respect to bond saturation and stereoisomerism have oxygen-containing functional groups in addition to the double or triple bonds. It seemed possible that some of the effects of bond saturation on perceived odor for these odorants (as compared to the hydrocarbons we studied previously) might involve an interaction between the recognition of oxygen-containing functional groups by odorant receptors and differences in the overall odorant molecule imparted by the unsaturated bond. To explore further the possible effects of double and triple bonds, we therefore investigated a number of sets of odorants with oxygen-containing functional groups that differed in the presence, type, number, location, and stereoisomerism of double and triple bonds (Table 2). This set of chemicals includes odorants that have been characterized as having differences in perceived odor (Table 1). We tested the hypothesis that these odorants would have differences in their evoked activity patterns despite the relative lack of effects involving hydrocarbons differing in the same parameters (Ho et al., 2006b). Table 2 Odorant exposures in this study1.