Hallkaj, J. | Search bioRxiv

bioRxiv2026

Odor representations are structured by heterogeneous tuning and concentration-dependence of functionally distinct olfactory sensory neuron subpopulations.

Olfactory stimuli (odorants) are represented by combinatorial patterns of olfactory sensory neuron (OSN) activation that are translated into spatially-organized glomerular maps at their input to the CNS. How glomerular maps relate to odorant features - including chemical structure and concentration - remains a key question in understanding the neural mechanisms of odor coding. Here, we compared glomerular response maps for the same 59 odorants across three concentration regimes, using GCaMP6 imaging from OSN axon terminals in the olfactory bulb (OB) of the anesthetized mouse. At the lowest regime, in which concentrations were chosen to distinguish the most sensitive glomeruli for each odorant, glomeruli were exceptionally narrowly tuned and responses across glomeruli were extremely sparse. We then compared responses at two higher-concentration regimes, 'low' and 'high', differing by 25-fold from each other and 2 - 5 log units higher than the 'most-sensitive' regime. Increasing concentration broadened tuning of OSN inputs; this broadening was heterogeneous across chemical space and was well-described by classifying glomeruli into several subpopulations with distinct consensus tuning profiles. Each subpopulation was selectively tuned to one or a few odorant chemical classes and spatially clustered in a manner consistent with the projection patterns of receptor-defined OSN classes. Glomerular subpopulations retained distinct tuning and spatial localization even at the highest concentrations. OSN subpopulations thus sample chemical space nonuniformly across a large concentration range. These results suggest a lower-dimensional structure in the representation of odorant information that largely reflects OSN subpopulations which, in turn, map to olfactory receptor subfamilies. This organization may enable distinct odor coding strategies for different OSN classes and for parts of chemical feature space with distinct ethological relevance.

neuroscience↗

bioRxiv2026

Rapid odorant metabolism organizes identity- and timing-based odor representations by olfactory bulb inputs and outputs

Sensory neurons encode information about external stimuli in the form of stimulus-specific patterns of activity across their population. In the mammalian olfactory system, olfactory sensory neurons (OSNs) encode odor identity with odorant-specific combinatorial patterns that are temporally structured by inhalation. We investigated the stimulus features that determine these inhalation-linked patterns, leveraging receptor- and functionally-defined OSN populations in awake mice. We found that both the chemical tuning and temporal dynamics of many odorant-evoked responses deviate from prevailing models of receptor-ligand binding and sensitivity-based timing relationships. These deviations were well-explained by rapid metabolism of odorants within the olfactory mucosa, which generates secondary odorants that activate additional OSNs within a single breath. This process fundamentally reshapes odor representations at naturally-occurring concentrations and timescales relevant to perception. Importantly, we found that timing features robustly discriminate inhaled from metabolism-generated odorants, and that these timing differences persist at the level of olfactory bulb output. Our results suggest a novel role for inhalation-linked timing in odor coding - to disambiguate inhaled odorants from those generated internally - and raise the possibility that the nervous system may differentially process external and internally-sourced olfactory stimuli on the basis of their temporal dynamics.

neuroscience↗