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Predictive Value of Activity Maps

The value of any scientific observation is perhaps best judged by whether it allows one to predict the outcome of future experiments. Our maps of odorant-evoked 2DG uptake across the glomerular layer of the olfactory bulb have been predictive in two senses: they have predicted aspects of the patterns that would be evoked by previously untested odorants, and they have predicted relative similarities in odors perceived by rats. 

The original associations between functional group-related molecular features and activity in particular anterior glomerular modules (Johnson and Leon, 2000a) successfully predicted that other simple aliphatic odorant chemicals possessing the same features also would stimulate those modules (Johnson et al., 2002; 2004). Aspects of glomerular activity patterns related to hydrocarbon structure also have had predictive value. The ventral shifts in activity that we observed with increasing carbon number for aliphatic, oxygen-containing odorants (Johnson et al., 1999, 2004) led us to predict that even larger straight-chained molecules might stimulate an extremely ventral portion of the bulb that we had not seen activated previously. We tested this prediction using very long alkanes such as pentadecane, which indeed activated the extreme ventral aspect (Ho et al., 2006a). We also predicted that this very long chain would evoke a similar ventral response in other molecules, such as a long straight-chained ketone and a long straight-chain ester of similar carbon number, indicating that the system regarded this hydrocarbon structure as a specific molecular feature, regardless of the functional group.  

 

As part of our effort to understand the relationships between odorant chemistry and bulbar activity patterns, we mapped responses to three pairs of odorant enantiomers: carvone, limonene, and terpinen-4-ol. Since these pairs of odorants differ in only one molecular feature, we predicted that if the pairs of enantiomers differed in their neural response (if the system recognized the specific stereoconfiguration as a feature), then the rats should discriminate between the enantiomers. Conversely, if there were no significant difference in the neural response, we predicted that the rats would not discriminate those enantiomers. We found that the patterns evoked by the two carvone enantiomers were much more distinct than those evoked by the other two pairs of enantiomers (Linster et al., 2001). This finding led us to predict that the odors of the carvone enantiomers might be more readily distinguished than those of the limonenes and terpinen-4-ols. Indeed, a cross-habituation assay revealed that rats spontaneously discriminated between the carvone enantiomers, but treated the limonene and terpinen-4-ol enantiomers as being similar in odor (Linster et al., 2001). The quantitative differences in our activity patterns across homologous series of acids and alkanes also correlated well with behavioral measures of odor discrimination (Cleland et al., 2002; Ho et al., 2006a). We have since found that quantitative differences in activity patterns for hydrocarbons differing in branch structure and bond saturation also are predictive of quantitative measures of odor discrimination (Ho et al., 2006b). It should be noted that the fine correlation between glomerular response and spontaneous odor perception was lost when rats were rewarded for their responses (Linster et al., 2002), since all odorants were discriminated under those conditions. 

Enantiomers of carvone showed a greater difference in evoked activity patterns than did enantiomers of limonene and terpinen-4-ol, which was correlated with spontaneous discrimination of the carvone enantiomers by rats.

 
 
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This Human Brain Project/Neuroinformatics project is funded by the National Institute on Deafness and Other Communication Disorders and the National Institute of Mental Health