A competitive binding model predicts nonlinear responses of olfactory receptors to complex mixtures

Abstract: In color vision, the quantitative rules for mixing lights to make a target color are well understood. By contrast, the rules for mixing odorants to make a target odor remain elusive. A solution to this problem in vision relied on characterizing the receptor responses to different wavelengths of light and subsequently relating receptor responses to perception. In olfaction, experimentally measuring the receptor response to a representative set of complex mixtures is intractable due to the vast number of possibilities. To meet this challenge, we develop a biophysical model that predicts mammalian receptor responses to complex mixtures using responses to single odorants. The dominant nonlinearity in our model is competitive binding: only one odorant molecule can attach to a receptor binding site at a time. This simple framework predicts receptor responses to mixtures of up to twelve monomolecular odorants to within 10-30% of experimental observations and provides a powerful method for leveraging limited experimental data. Simple extensions of our model describe phenomena such as synergy, overshadowing, and inhibition, suggesting that these perceptual effects can arise partly from receptor binding properties, and may not require either complex neural interactions or feedback from higher brain areas.