Predicting odorant quality perceptions from multidimensional scaling of olfactory bulb glomerular activity patterns.

The first step in the encoding of an odorant appears to be mediated by the binding of odorant molecular features to odorant receptors on olfactory sensory neurons (OSNs) (Malnic et al., 1999). Odorants stimulate distinct patterns of activity in the olfactory epithelium (Moulton, 1976; Scott & Brierly, 1999; Youngentob et al., 1995) that accurately predict psychophysically determined odorant quality perception (Kent et al., 1995, 2003). By virtue of the highly organized OSN projections to the bulb (Mombaerts, 1996), the information displayed by glomeruli is a reflection of the OSN responses (Johnson & Leon, 2000a,b; Johnson et al., 1998, 1999, 2002, 2005a,b; Uchida et al., 2000). Therefore, it has been hypothesized that odorant quality is represented through patterns of glomerular activation that enhance the patterned information established in the differential activation of OSNs (Kent et al., 2003; Mori et al., 1999; Youngentob et al., 1995). Consistent with this view are functional imaging studies demonstrating odorant specific patterns of glomerular activity (Johnson & Leon, 2000a,b; Johnson et al., 1998, 1999, 2002, 2005a,b; Meister & Bonhoffer, 2001; Uchida et al., 2000; Xu et al., 2003). Also suggestive are behavioral observations demonstrating that bulbar patterns of [14C]-2-deoxyglucose (2-DG) glomerular uptake predict the differential ability of rats to perceive two chemically similar stimuli as different in an olfactory habituation/dishabituation task (i.e., enantiomer pairs [Linster et al., 2001], homologous series [Cleland et al., 2002; Ho et al., 2006a] or similar hydrocarbons [Ho et al., 2006b]). The above notwithstanding, the molecules, neural responses, and perceptions involved in olfaction are by their nature multidimensional. Indeed, one odorant can be described as being similar to two other odorants, and yet these two other odorants may not be perceived as correspondingly similar to each other. For this reason, studies of human olfactory perception have very commonly involved multidimensional techniques such as multidimensional scaling or principal components analysis to describe the relationships between odor perceptions more thoroughly (Chastrette et al., 1991; Dawes et al., 2004; Doty et al., 1994; Madany Mamlouk et al., 2003; Schiffman et al., 1977; Stevens and O’Connell, 1996). Odorant chemistry and the patterns of activity evoked by odorants in the rat olfactory bulb typically also differ simultaneously along many dimensions (Farahbod et al., 2006), and it is reasonable to expect that a complete understanding of the relationships between neural activity and perception would involve many of these dimensions. Indeed, relationships between odorants revealed by multidimensional scaling of perceptual similarities derived using a five-odorant identification confusion matrix task are well predicted by relationships revealed by multidimensional scaling of olfactory epithelial activity pattern similarities in rats (Kent et al., 1995, 2003; Youngentob et al., 2001). To date, most investigations of the relationships between bulbar activity patterns and behavior have involved systematic differences along single dimensions of odorant chemistry such as stereoconfiguration in enantiomer odorants and carbon chain length in homologous series of odorants (Linster et al., 2001; Cleland et al., 2002; Ho et al., 2006a,b). To test the possibility of a multidimensional relationship among bulbar activity patterns and odor perception, we have used in the present study a set of five odorants that cannot be classified as a group that varies along a single chemical dimension. These odorants are acetone, 2-propanol, santalol, β-pinene, and pentadecane (Fig. 1). In this respect, although acetone and 2-propanol share a simple three-carbon backbone, 2-propanol also shares an alcohol functional group with santalol. Santalol and β-pinene are both polycyclic compounds, while β-pinene and pentadecane are both hydrocarbons without oxygen-containing functional groups. Pentadecane and santalol, on the other hand, are similar in their larger carbon number. Consequently, because both hydrocarbon structure and functional groups have been identified as important structural determinants of bulbar activity patterns (Johnson et al., 2002, 2005a; Leon and Johnson, 2003), it is not possible to predict, a priori, which odorant pairs would produce the most similar activity patterns. Indeed, as outlined below, the activity patterns evoked by these five odorants overlap in different bulbar locations depending on the different chemical relationships between the compounds Figure 1 Chemical structures of the five odorants studied. In this study, we show that 2-DG spatial patterns of odorant-evoked glomerular activity (Johnson & Leon, 2000a,b) accurately predict odorant quality perceptual patterns resulting from an odorant identification confusion matrix task that directly extracts perceptual quality relationships across sets of odorants (Kent et al., 1995, 2003; Youngentob et al., 1990, 1991, 2001).