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

Abstract

Many naturally occurring volatile chemicals that are detected through the sense of smell contain unsaturated (double or triple) carbon-carbon bonds. These bonds can impact 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 versus trans configuration had no measurable impact in all five sets of stereoisomers 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. Keywords 2-deoxyglucose; odors; imaging techniques; mappingWe 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., 1998Johnson et al., , 1999Johnson et al., , 2002Johnson et al., , 2004Johnson et al., , 2005aJohnson et al., ,b, 2006Linster 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 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript able to identify a number of molecular features that are particularly important in determining the response specificity of particul...

Chemotopic odorant coding in a mammalian olfactory system

“…Carboxylic acids possessing a great variety of hydrocarbon structures (straight-chained from 2-11 carbons, double-bonded, branched, and cyclic) all stimulate glomeruli in a pair of anterior domains that are shaded orange in Figure 4 (Johnson et al, 1999;2002;2007a;Johnson and Leon, 2000b;and unpublished observations). Examples of effective odorants include propionic acid, valeric acid, and undecylenic acid.…”

“…For example, although double and triple bonds have unique partial charge distributions and steric configurations that presumably could serve as distinctive binding sites for sets of odorant receptors, odorants sharing such features do not specifically overlap in their stimulation of particular glomeruli (Ho et al, 2006b;Johnson et al, 2007a). Instead, unsaturated bonds seem either to disrupt the recognition of certain odorant ligands by certain receptors or to change the glomeruli that are activated within a module (Ho et al, 2006b;Johnson et al, 2007a). Another example is certain cyclic structures, which would seem to provide enough specific chemical "information" to support recognition by a class of odorant receptors, but which do not activate common glomeruli .…”

“…More generally, some chemical attributes appear to have greater importance in determining responses than others, just as some odorants seem to evoke more overall activity than others (Johnson and Leon, 2000b;Ho et al, 2006b;Johnson et al, 2006;2007a). The olfactory system evolved to solve biologically relevant problems under certain constraints, and an all-purpose qualitative analysis of odorant chemistry would not be expected of the system, which is more likely to be focused on sets of odorant chemicals that contribute important information relevant to survival and reproduction.…”

“…Instead, the aromatic feature trumps that response and activity is confined to the posterior, dorsal domain responding to benzyl odorants with oxygenic substituents (Johnson et al, 2005b;Farahbod et al, 2006). Another example is that glomerular responses related to oxygenic functional groups can be hindered if alicyclic structures (Johnson et al, 2007b) or triple bonds (Johnson et al, 2007a) are located near the functional group in the odorant molecule, perhaps because the hydrocarbon feature interferes with the proper positioning of the odorant functional group at the receptor binding site (Araneda et al, 2000).…”

“…A pair of glomerular domains located just posterior and slightly ventral relative to the acidpreferring modules (green-shaded areas in Figure 4) contains principal responses to primary alcohols with various hydrocarbon structures, including straight-chained, simple branched, and double-bonded molecules such as 1-pentanol, 4-methyl-1-pentanol, and trans-2-hexen-1-ol (Johnson and Leon, 2000a;Johnson et al, 2002;2004;2005a;2007a), as well as relatively weaker responses to straight-chained aliphatic aldehydes and ketones (Johnson and Leon, 2000a;Johnson et al, 2002;2004). These same areas contain responses to phenols, which are aromatic odorants substituted with hydroxyl groups, resembling alcohols in that respect, and including spicy odorants such as vanillin and eugenol as well as smoky odorants such as guaiacol Farahbod et al, 2006).…”