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.