Odor maps in the dorsal and lateral surfaces of the rat olfactory bulb.

The surface of the mammalian olfactory bulb (OB) is covered by numerous glomeruli. Since individual glomeruli represent a single odorant receptor (OR) among a repertoire of nearly 1000 ORs, the spatial assembly of the glomeruli forms the maps of ORs. How are the numerous ORs represented spatially in the glomerular maps? Studies of mapping of odorant-induced glomerular activity using the optical imaging or fMRI methods showed that individual glomeruli responded to a range of odorants and that the range differed widely among different glomeruli. In the present series of experiments, we determined the molecular receptive range (MRR) of individual glomeruli in the rat OB using the method of optical imaging of intrinsic signals and systematic panels of ~70 stimulus odorants. Based on the MRR property, we deduced the characteristic molecular features that were shared by odorants effective in activating individual glomeruli (Takahashi et al., 2004). Examination of the spatial representation of MRRs in a substantial part of the glomerular map would provide the basic knowledge of the spatial representation of the ORs in the glomerular maps. Detailed analysis of MRRs of individual glomeruli in the dorsal area (mostly zone 1) of the OB indicated that glomeruli having similar and overlapping MRRs gathered in close proximity and formed ‘molecular-feature clusters’. Cluster A glomeruli were located at the anteromedial part of the dorsal surface. The characteristic molecular-features of odorants effective in activating the cluster A glomeruli are a carboxyl group {–COOH}, a diketone group {–(CO)(CO)–} or an ester group {–(CO)O–}, functional groups having two oxygen atoms in a neighborhood. In addition, odorants having a single aldehyde group {–CO} or an amino group {–NH2} at the end of the molecule were effective in activating many glomeruli in cluster A. Cluster B was located in the most anterior region of the lateral part of the dorsal surface. The characteristic molecular features of cluster B glomeruli were elongated carbon chain structure with a hydroxyl group {–OH}, an alkoxyl group {–O-R} or a carbonyl group {–CO} (in ketones) attached at one side of the molecule. Cluster C was located at the central region of the lateral part of the dorsal surface. The characteristic molecular features of glomeruli in the cluster C include the combination of the benzene-ring-like hydrocarbon structure and a hydroxyl group, a methoxy group, or an ethoxy group. Cluster D glomeruli were located at the caudal part of the dorsal OB. Odorants effective in activating the cluster D glomeruli were mainly ketones: cyclic ketones, aliphatic–aromatic ketones, diketones, and a subset of aliphatic ketones with relatively short side chains. Immunohistochemical staining of OB sections with an antiOCAM antibody indicated that clusters A–D were located in zone 1 of the lateral map. Although both of the overall molecular shape and the functional group(s) were important determinants in activating individual glomeruli in clusters A–D, the characteristic molecular features common to the glomeruli in each cluster were one or more oxygenor nitrogen-containing functional groups. This suggests that the presence and the position of functional group(s) in the odorant molecular structure play a key role in activating the glomeruli in clusters A–D. Hydrocarbon odorants lack a hetero-atom-containing functional group. Except for a few scattered glomeruli, hydrocarbon odorants did not activate glomeruli in clusters A–D in zone 1. In a striking contrast, hydrocarbon odorants activated many glomeruli in clusters F and G, which were located outside of zone 1. Although these glomeruli responded to a relatively wide range of odorants with and without functional group(s), the characteristic molecular features of cluster F glomeruli included the terpene hydrocarbon structure, while those of cluster G were benzene-family hydrocarbons. Hydrocarbon odorants activated glomeruli also in the lateroventral surface of the OB, which were in zones 2–4. Thus the clusters of hydrocarbon-responsive glomeruli were located mostly in zones 2–4.