To study the mechanism whereby odorants are encoded in the nervous system, we studied the glomerular-layer activity patterns in the rat olfactory bulb evoked by closely related odorants from different chemical families. These odorants had a common straight-chain hydrocarbon structure, but differed systematically in their functional groups. Neural activity was mapped across the entire glomerular layer by using the ¿(14)C2-deoxyglucose method. Group responses were averaged and compared by using data matrices. The glomerular activity patterns that resulted from this analysis were comprised of modules. Unique combinations of modules were activated by each odorant, demonstrating what may be part of the neural code for odorants. Most of the modules were clustered together in the bulb, perhaps providing for enhanced contrast between related chemicals by means of lateral inhibition. We also determined whether changes in odorant concentration would affect spatial patterns of glomerular activity. Two odorants, pentanal and 2-hexanone, evoked different patterns at increased concentrations, with additional glomeruli being recruited at a great distance from glomeruli in which activity was evoked at lower concentrations. Humans report that both of these odorants change in perceived odor with increasing concentration. Three other odorants (pentanoic acid, methyl pentanoate, and pentanol) did not recruit new areas of glomerular activation with increasing concentration, and humans do not report a changed odor across concentrations of these odorants. The results suggest that changes in modular glomerular activity patterns could underlie altered odor perception across odorant concentrations, and they provide additional support for a combinatorial, spatially based code in the olfactory system.

In an effort to understand the means by which similar chemical odorants are encoded in the mammalian brain, we exposed rats to a homologous series of n‐aliphatic acids and mapped the response of the entire olfactory bulb glomerular layer by using a high‐resolution [14C]‐2‐deoxyglucose uptake technique. We found that these similar odorants evoked spatially clustered but distinct responses in the bulb that changed systematically with carbon chain length. In addition to these chemotopic responses, different odorants within the series evoked systematic differences along two other dimensions: amount of deoxyglucose uptake and extent of the glomerular layer showing high activity. Increases along these two dimensions also were correlated with increasing carbon number. The focal glomerular responses were mirrored by responses in deeper bulb layers. Decreasing the odorant concentration decreased the deoxyglucose uptake within focal regions. The focal regions of activity occurred in pairs involving both medial and lateral representations in the bulb, perhaps reflecting the paired medial and lateral projections of olfactory sensory neurons expressing specific types of odorant feature receptor proteins. The observed spatial pattern of response also may explain both the failure of some bulb lesions to interfere with behavioral olfactory responses and the success of other lesions in blocking olfactory responses. These data support a model of parallel, distributed processing of odorants along multiple dimensions. They also support the notion that analyses of the spatial relationships among odorant responses in the olfactory bulb can demonstrate aspects of the mechanism for odor chemical coding. J. Comp. Neurol. 409:529–548, 1999. © 1999 Wiley‐Liss, Inc.

Systematic mapping studies involving 365 odorant chemicals have shown that glomerular responses in the rat olfactory bulb are organized spatially in patterns that are related to the chemistry of the odorant stimuli. This organization involves the spatial clustering of principal responses to numerous odorants that share key aspects of chemistry such as functional groups, hydrocarbon structural elements, and/or overall molecular properties related to water solubility. In several of the clusters, responses shift progressively in position according to odorant carbon chain length. These response domains appear to be constructed from orderly projections of sensory neurons in the olfactory epithelium and may also involve chromatography across the nasal mucosa. The spatial clustering of glomerular responses may serve to "tune" the principal responses of bulbar projection neurons by way of inhibitory interneuronal networks, allowing the projection neurons to respond to a narrower range of stimuli than their associated sensory neurons. When glomerular activity patterns are viewed relative to the overall level of glomerular activation, the patterns accurately predict the perception of odor quality, thereby supporting the notion that spatial patterns of activity are the key factors underlying that aspect of the olfactory code. A critical analysis suggests that alternative coding mechanisms for odor quality, such as those based on temporal patterns of responses, enjoy little experimental support.

Postnatal olfactory learning produces both a conditioned behavioral response and a modified olfactory bulb neural response to the learned odor. The present report describes the role of norepinephrine (NE) on both of these learned responses in neonatal rat pups. Pups received olfactory classical conditioning training from postnatal days (PN) 1-18. Training consisted of 18 trials with an intertrial interval of 24 hr. For the experimental group, a trial consisted of a pairing of unconditioned stimulus (UCS, stroking/tactile stimulation) and the conditioned stimulus (CS, odor). Control groups received either only the CS (Odor only) or only the UCS (Stroke only). Within each training condition, pups were injected with either the NE beta-receptor agonist isoproterenol (1, 20, or 4 mg/kg), the NE beta-receptor antagonist propranolol (10, 20, 40 mg/kg), or saline 30 min prior to training. On day 20, pups received one of the following tests: (1) behavioral conditioned responding, (2) injection with 14C-2-deoxyglucose (2-DG) and exposed to the CS odor, or (3) tested for olfactory bulb mitral/tufted cell single-unit responses to the CS odor. The results indicated that training with either: (1) Odor-Stroke-Saline, (2) Odor-Stroke-Isoproterenol-Propranolol, or (3) Odor only-Isoproterenol (2 mg/kg) was sufficient to produce a learned behavioral odor preference, enhanced uptake of 14C-2-DG in the odor-specific foci within the bulb, and a modified output signal from the bulb as measured by single-cell recordings of mitral/tufted cells. Moreover, propranolol injected prior to Odor-Stroke training blocked the acquisition of both the learned behavior and olfactory bulb responses. Thus, NE is sufficient and may be necessary for the acquisition of both learned olfactory behavior and olfactory bulb responses.

In an effort to understand the olfactory code of rats, we collected more than 1,500,000 measurements of glomerular activity in response to 54 odorants selected to provide differences in functional groups and hydrocarbon structure. Each odorant evoked a unique response pattern by differentially stimulating clusters of glomeruli, called modules. Odorants sharing specific aspects of their structure activated the same modules, allowing us to relate responses to structure across approximately 80% of the glomerular layer. The most obvious relationship was between the presence of particular oxygen-containing functional groups and the activity of glomeruli within dorsal modules. Functional group-specific responses were observed for odorants possessing a wide range of hydrocarbon structure, including aliphatic, cyclic, and aromatic features. Even formic acid and acetone, the simplest odorants possessing acid or ketone functional groups, respectively, stimulated modules specific for these functional groups. At the same time, quantitative analysis of pattern similarities revealed relationships in activation patterns between odorants of similar hydrocarbon structure. The odorant responses were reliable enough to allow us to predict accurately specific aspects of odorant molecular structure from the evoked glomerular activity pattern, as well as predicting the location of glomerular activity evoked by novel odorants.