Stable olfactory receptor activation across odor complexity

Mechanisms underlying single odorant activation of specific olfactory receptors are well understood. However, how the olfactory system processes complex odor mixtures at the receptor level remains unclear. This study examined olfactory receptor activation patterns across odor complexities using phosphoTRAP analysis. For most mixtures, receptor activation patterns closely matched the linear sum of individual component responses. However, distinct receptor sets display non-linear responses unexplained by linear models. Mixture responses were generally located between component responses and often aligned with linear predictions, though some deviations indicated non-linear interactions. Total activated receptors remained relatively constant regardless of odor complexity, suggesting efficient coding that prevented receptor saturation as odorant components increased. These findings provide receptor-level evidence that the olfactory system encodes complex odors primarily through linear integration of receptor activity, with added specificity from non-linear responses in limited receptors, advancing understanding of how the olfactory system normalizes receptor activation in response to natural odors.