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

Studies by a number of laboratories using odorants that differ systematically in molecular structures continue to support a combinatorial model of olfactory processing initially proposed by Polak (1973), in which molecular features of an odorant are recognized and encoded by the system (Kauer and Cinelli, 1993; Friedrich and Korsching, 1997, 1998; Joerges et al., 1997; Johnson et al., 1998, 1999, 2002, 2004, 2005a, b; Malnic et al., 1999; Rubin and Katz, 1999; Sachse et al., 1999; Johnson and Leon, 2000a, b; Uchida et al., 2000; Belluscio and Katz, 2001; Fuss and Korsching, 2001; Meister and Bonhoeffer, 2001; Igarashi and Mori, 2005). According to this model, odorants that share a molecular feature should be recognized by the same type of olfactory receptors to produce overlapping neural activity. To test this prediction, and to understand how the olfactory system responds to various molecular features, our laboratory has been studying responses to hundreds of odorants in the glomerular layer of the rat main olfactory bulb (Johnson et al., 1998, 1999, 2002, 2004, 2005a, b; Johnson and Leon, 2000a, b; Linster et al., 2001a). In an effort to understand the processing of pure hydrocarbon structures in this system, we determined in this study the response to a series of alkanes, which are straight-chained hydrocarbons without functional groups. The responses to the odorants studied thus far collectively involve most of the glomerular layer, with the marked exception of an area in the midventral region. From studies of numerous homologous series of odorants up to eleven carbons in the chain, it was clear that larger odorants systematically evoked responses that were progressively ventral (Johnson et al., 1999, 2004; Johnson and Leon, 2000b). We therefore hypothesize that the previously unresponsive ventral area might respond to even larger odorants than we had yet studied (Johnson et al., 2002). Since straight-chained alkanes remain volatile even at great molecular length, we used the [14C]2-deoxyglucose (2-DG) method developed by our laboratory to examine glomerular responses to a homologous series varying from six to sixteen carbons, and predicted that responses to the larger odorants in this series would be observed in the mid-ventral area of the bulb. Even though glomerular responses have been observed to be organized topographically and have been found to be correlated with a number of molecular features of odorous stimuli (Imamura et al., 1992; Katoh et al., 1993; Friedrich and Korsching, 1997, 1998; Joerges et al., 1997; Johnson et al., 1998, 1999, 2002, 2004, 2005a, b; Johnson and Leon, 2000a, b; Fuss and Korsching, 2001; Meister and Bonhoeffer, 2001; Takahashi et al., 2004; Igarashi and Mori, 2005), it remains unclear whether such chemotopic information is maintained through downstream perceptual processing, so that odorant-evoked responses in the olfactory bulb would predict perceptual phenomena such as odor recognition and discrimination. Indeed, few studies have examined directly the relationship between the similarity of overall glomerular responses and perceived odor similarity (Linster et al., 2001a; Cleland et al., 2002). Nevertheless, these studies have shown a high correlation between the evoked glomerular patterns and odor perception. Aspects of odorant chemistry also have been found to correlate with odor discriminability in a number of psychophysical studies (Laska and Freyer, 1997; Laska and Teubner, 1999; Laska et al., 1999, 2000; Linster and Hasselmo, 1999; Laska and Galizia, 2001; Laska and Hubener, 2001; Linster et al., 2001a, b; Cleland et al., 2002). Together, these results suggest a close and predictable relationship among odorous stimuli, glomerular responses and perceived odors. In all of these cases, however, the odorants used involved molecules with oxygen-containing functional groups, which are well known to have profound impact on perceived odor. In fact, aliphatic odorants containing the same oxygen-containing functional group were found to be discriminable even with just a one-carbon difference in their chain length (Laska and Freyer, 1997; Laska and Teubner, 1999; Laska et al., 1999; Linster and Hasselmo, 1999; Laska and Galizia, 2001; Laska and Hubener, 2001; Cleland et al., 2002). Odorants possessing oxygen-containing functional groups can interact with receptors by way of hydrogen bonds. In contrast, alkane odorants can only interact with receptors by way of Van der Waals forces, which are much weaker than hydrogen bonds. The weakness of these interactions would be expected to result in low-affinity binding. Given the likelihood of low-affinity receptor binding, it was not clear whether the pattern of glomerular activity evoked by these alkane odorants would reveal the same degree of specificity that has characterized the patterns evoked by the numerous oxygen-containing odorants that we have studied previously. It also was not clear whether these alkanes would be perceived to have significantly distinct odors. Indeed, these odorants often are given the same “gasoline-like” odor description by humans (see, for example, http://hazmap.nlm.nih.gov/). Therefore, we investigated the triad relationships among odorant chemistry, bulbar activation patterns, and perceived odors using a homologous series of pure alkanes.