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

Various aspects of odorant chemistry are encoded by the rat olfactory system to produce chemotopically organized responses in the olfactory bulb (Imamura et al., 1992; Katoh et al., 1993; Joerges et al., 1997; Johnson et al., 1998, 1999, 2002, 2004, 2005a, b; Rubin and Katz, 1999; Johnson and Leon, 2000a, b; Uchida et al., 2000; Linster et al., 2001; Meister and Bonhoeffer, 2001; Igarashi and Mori, 2005; Ho et al., 2006). Comparable chemotopic organization also has been observed in other animal species (Kauer and Cinelli, 1993; Friedrich and Korsching, 1997, 1998; Sachse et al., 1999; Belluscio and Katz, 2001; Fuss and Korsching, 2001; Carlsson et al., 2002; Fried et al., 2002; Kent et al., 2003). Thus far, these observations have been obtained mostly through using odorants with oxygen-containing functional groups that are known to have a profound impact on perceived odors (Laska and Freyer, 1997; Laska and Teubner, 1999; Laska et al., 1999, 2001; Linster and Hasselmo, 1999; Laska and Galizia, 2001; Laska and Hubener, 2001; Cleland et al., 2002). Recently, we showed that the system also was differentially responsive to a homologous series of straight-chained aliphatic alkanes consisting of purely hydrocarbon structures (Ho et al., 2006). Even though these alkanes could bind to olfactory receptors only by way of weak Van der Waals forces, they evoked highly specific glomerular response patterns that were found to be significantly different for alkanes of different carbon number. In addition, rats were able to discriminate spontaneously among pairs of these odorants that differed by as little as one carbon in the carbon chain, although humans report their odors to be quite similar. Progressively changing carbon chain length across a homologous series is only one way to vary hydrocarbon structures systematically. More subtle chemical differences exist for isomeric chemicals, which possess identical molecular formulae, but which have different molecular arrangements that could result in distinct molecular shapes and properties that might be recognized by specific odorant receptors. Such structural variations include positional isomers where functional groups or alkyl groups are present at different locations along the carbon backbone of aliphatic molecules. Indeed, significantly different glomerular activity patterns were detected for some, but not all, isomeric aliphatic odorants that had the same oxygen-containing functional groups at different positions along the hydrocarbon chain (Johnson et al., 2005a). We also have observed small differences in glomerular responses to enantiomeric odorants (Linster et al., 2001). However, not all enantiomeric odorant pairs tested in that study were discriminated spontaneously by the animals (Linster et al., 2001), indicating that small differences in glomerular responses may contribute to the discrimination of only some odorants. Therefore, it is unlikely that all of the small differences observed in glomerular responses are equally relevant to all perceptual processes. Another type of structural variation that has not yet been investigated systematically in studies of olfactory coding involves the nature of carbon-carbon bonds present in an odorant molecule. Double and triple bonds confer distinct bond angles and geometries (Fig. 1), reduce flexibility, and offer the potential of stronger interactions through hydrogen bonding (Fig. 2). In fact, unsaturated alkenes (double-bonded) and alkynes (triple-bonded) do have very different molecular properties (Fig. 2) and are chemically more reactive than their parent alkanes. Figure 1 Molecular structures of the eight-carbon isomeric branched alkanes, octenes, and octynes, some of which have greatly different molecular shapes from the unbranched and saturated octane. Carbon and hydrogen atoms are represented by gray and blue solid ... Figure 2 Stacked bar graphs showing that the molecular property profiles of individual hydrocarbon odorants are distinct from each other. Each molecular property of individual odorants was expressed as a ratio of the sum of values obtained from all odorants tested ... In the present study, we first examined both glomerular and perceptual responses to branched-chain isomers of octane (Fig. 1) to investigate systematically the impact of branching in pure hydrocarbon structures with no oxygen-containing functional groups. In addition, we studied responses to a group of eight-carbon unsaturated hydrocarbons to determine how the system may respond to changes in bond saturation. It should be noted that unsaturated bonds are considered to be functional groups, and we chose to examine their effects on olfactory responses without the influence of any other functional groups by using various eight-carbon octenes and octynes (Fig. 1). Although odorants with structures that are more closely related to each other have more similar molecular property profiles in general, as demonstrated by neighboring members in a homologous series such as the straight-chained alkanes (Fig. 2), individual odorants involving different branching and bond types display characteristic property profiles that are distinct from each other. Given that significantly different glomerular activity patterns and perceived odors were observed among odorants as molecularly related to each other as neighboring alkanes (Ho et al., 2006), we expected to find robust differences in neural and perceptual responses to the branched and unsaturated hydrocarbons that we tested in this study.