Distributed representation of chemical features and tunotopic organization of glomeruli in the mouse olfactory bulb

Abstract

In the mammalian brain, similar features of the sensory stimuli are often represented in proximity in the sensory areas. However, how chemical features are represented in the olfactory bulb has been controversial. Questions have been raised as to whether specific chemical features of the odor molecules are represented by spatially clustered olfactory glomeruli. Using a sensitive probe, we have analyzed the glomerular response to large numbers of odorants at single glomerulus resolution. Contrary to the general view, we find that the representation of chemical features is spatially distributed in the olfactory bulb with no discernible chemotopy. Moreover, odor-evoked pattern of activity does not correlate directly with odor structure in general. Despite the lack of spatial clustering or preference with respect to chemical features, some structurally related odors can be similarly represented by ensembles of spatially distributed glomeruli, providing an explanation of their perceptual similarity. Whereas there is no chemotopic organization, and the glomeruli are tuned to odors from multiple classes, we find that the glomeruli are hierarchically arranged into clusters according to their odor-tuning similarity. This tunotopic arrangement provides a framework to understand the spatial organization of the glomeruli that conforms to the organizational principle found in other sensory systems.

An electroolfactogram study of odor response patterns from the mouse olfactory epithelium with reference to receptor zones and odor sorptiveness

“…In contrast, the concept of chemotopy posits a systematic spatial representation in the olfactory system of some odorant feature such as carbon chain length or functional group (reviewed by Mori et al 2006). While a great deal of evidence from a number of different laboratories (reviewed by Johnson and Leon 2007;Murthy 2011) using relatively low-resolution techniques support this canonical hypothesis, more recent high-resolution analyses suggest that even crude chemotopy does not exist in the olfactory bulb (Ma et al 2012; reviewed by Murthy 2011). Indeed, a serious theoretical problem plagues the notion of spatial organization in the olfactory system: it is not clear how olfaction's tremendously high-dimensional stimulus space, entailing tens of thousands of odorants each with thousands of different physiochemical features (shape, size, polarity, etc.)…”

Multiplex assessment of the positions of odorant receptor-specific glomeruli in the mouse olfactory bulb by serial two-photon tomography

“…Because the entire sample is imaged intact, the results are not dependent on the orientation of the sample or the cutting plane. Importantly, our method covers all ∼3,600 glomeruli of the olfactory bulb, in contrast to functional imaging, which is confined to the dorsal olfactory bulb and covers only ∼200 glomeruli (33). Finally, our method is based on commercially available imaging equipment and software.…”

Odorant similarity in the mouse olfactory bulb

“…After applying ultra-high-resolution calcium-indicator dependent imaging to the olfactory bulb, Ma et al (4) failed to identify a correlation between odorant pairwise structural differences and pairwise neuronal response differences [ figure 4E in Ma et (5). To estimate whether these decisions contributed to the lack of correlation reported by Ma et al, we repeated the full analysis.…”