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Brann, J. H.

Publications and source records attributed to Brann, J. H..

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Evidence of elemental encoding at the olfactory periphery

How complex, multifaceted perceptual odor qualities of volatile chemicals are encoded by the olfactory system is poorly understood. We explore the receptive fields of individual odorant receptors and show how potent agonists share a consistent perceptual quality despite chemical diversity. This supports the idea that the olfactory neural connectome maintains peripheral information like odor quality through the distinct layers of the system, akin to a labeled line regime present in other sensory structures. We further observe that simple combinatorial activation of odorant receptors can generate a perceptual sum. Human olfaction may thus be shaped by the orthogonal and elemental encoding of olfactory features detected by receptor selectivity and activity. These results provide novel insights into how the brain processes olfactory information and more broadly into neural encoding during sensory processing.

neuroscience↗

ODORANT RECEPTOR INHIBITION IS FUNDAMENTAL TO ODOR ENCODING

Most natural odors are complex mixtures of many volatile components, competing to bind odorant receptors (ORs) expressed in olfactory sensory neurons (OSNs) of the nose. To date surprisingly little is known about how OR antagonism shapes neuronal representations in the periphery of the olfactory system. Here, we investigated its prevalence, the degree to which it disrupts OR ensemble activity, and its conservation across related ORs. Calcium imaging microscopy of dissociated OSNs revealed significant inhibition, often complete attenuation, of responses to indole, a commonly occurring volatile associated with both floral and fecal odors, by a set of 36 tested odorants. To confirm an OR mechanism for the observed inhibition, we performed single-cell transcriptomics on OSNs that exhibited specific response profiles to a diagnostic panel of odorants and identified the receptor Olfr743 which, when tested in vitro, recapitulated ex vivo responses. We screened ten ORs from the Olfr743 clade with 800 perfumery-related odorants spanning a range of chemical scaffolds and functional groups, over half of which (430) antagonized at least one of the ten ORs. Furthermore, OR activity outcomes were divergent rather than redundant, even for the most closely related paralogs. OR activity fitted a mathematical model of competitive receptor binding and suggests that normalization of OSN ensemble responses to odorant mixtures is the rule rather than the exception. In summary, we observed OR antagonism, inverse agonism and partial agonism occurring frequently and in a combinatorial manner. Thus, extensive receptor-mediated computation of mixture information appears to occur in the olfactory epithelium prior to transmission of odor information to the olfactory bulb.

neuroscience↗