Chemotopy refers to any systematic spatial representation of odorant chemistry. We have been particularly interested in determining whether the olfactory system uses this kind of spatial organization in the coding of odorants. Indeed, we have found that glomeruli of related specificity seem to be arrayed systematically within many glomerular modules. Uptake of 2-DG in the medial, acid-sensitive glomerular module shifted ventrally with increasing carbon number in a series of straight-chained carboxylic acids (Johnson et al., 1999). In the corresponding lateral module, uptake shifted both rostrally and ventrally. Separate focal responses in the more posterior part of both the lateral and the medial bulb also shifted ventrally with increasing carbon number in carboxylic acids. By using a homologous series of carboxylic acids of the same carbon number, but with different hydrocarbon structures (e.g., double-bonded, branched, and cyclic), we concluded that the ventral shift in the medial acid-responsive module correlated best with molecular length as opposed to hydrophobicity or volume (Johnson and Leon, 2000b).  

Recently, we found progressions of activity in the ventral direction with increasing odorant carbon number using aldehydes, esters, acetates, primary alcohols, secondary alcohols, and ketones in the glomerular regions that are differentially sensitive to these odorants, suggesting that such chemotopic progressions represent a fundamental organizational principal in the olfactory system (Johnson et al., 2004). More recently, we observed ventrally shifting activity with increasing carbon number in a homologous series of alkanes, which lack functional groups altogether (Ho et al., 2006a).  

Why are the chemotopic progressions with increasing carbon number always in the ventral direction? One possibility is that the chemotopic progressions are related to the spatial distributions of the odorants themselves across the olfactory epithelium. Maxwell Mozell and his collaborators showed that odorants partition across the frog epithelium chromatographically (Mozell, 1964; Hornung and Mozell, 1977; Mozell et al., 1987). Molecules that are more water-soluble (hydrophilic) absorb more readily into the olfactory mucosa, a situation that would prevent them from reaching the more peripheral and ventral parts of the rat epithelium (Schoenfeld and Knott, 2004). The less water-soluble (more hydrophobic) odorant molecules would be freer to distribute across the epithelium to reach the more peripheral and ventral zones. Longer odorants within any homologous series of straight-chained chemicals would be more hydrophobic and therefore would be expected to penetrate into the peripheral and ventral epithelium. Because the more peripheral and ventral regions of the epithelium project to more ventral bulbar targets (Schoenfeld et al., 1994; Schoenfeld and Knott, 2002), this topography could explain the ventral chemotopic progressions within many glomerular modules in the olfactory bulb (Johnson et al., 2004).  

Increasingly hydrophobic molecules may absorb less readily within the olfactory mucosa, allowing them to interact with receptors located in the more peripheral portions of the epithelium, which project to more ventral glomeruli (from Schoenfeld and Knott, 2004).

Local bulbar anatomy suggests that chemotopic progressions in the glomerular layer might have important functional consequences. Reciprocal synapses between mitral cell projection neurons and inhibitory interneurons in the glomerular layer (periglomerular neurons and so-called short-axon cells) and in the external plexiform layer (granule cells) are expected to create local lateral inhibitory networks. Strong activity in mitral cells associated with a given glomerulus would likely suppress activity in less strongly stimulated mitral cells associated with neighboring glomeruli (Mori and Shepherd, 1994; Aungst et al., 2003). This pattern of activity would be predicted to "tune" or decorrelate mitral cell activity, so that individual mitral cells would be excited by a more narrow range of molecules than would excite individual sensory neurons. Indeed, pharmacological blockade of inhibition in the bulb widens the molecular receptive range of mitral cells (Yokoi et al., 1995). Chemotopic progressions insure that the glomeruli that are nearest neighbors within a module would have the most similar specificity within a homologous series, thereby insuring that tuning involves the most similar odorant molecules.