Competitive binding 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 receptor responses to different wavelengths of light and subsequently relating these responses to perception. In olfaction, experimentally measuring receptor responses 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 (CB): 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 12 monomolecular odorants to within 15% 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. We demonstrate that the presence of such interactions can be identified via systematic deviations from the competitive-binding model.

Hyperbolic odorant mixtures as a basis for more efficient signaling between flowering plants and bees

“…Both properties would enhance the accuracy and speed of detectability of mixtures over pure odorants. Competitive binding in mixtures can also predict more complex properties of sensory receptor responses, such as synergy, antagonism and overshadowing (Reddy, Zak, Vergassola, & Murthy, 2018;Singh, Murphy, Balasubramanian, & Mainland, 2019).…”

Antagonistic odor interactions in olfactory sensory neurons are widespread in freely breathing mice

“…Recent theoretical work has shown that a variety of non-linear interactions among multiple ligands at the same receptor can readily arise with a simple two-step model of receptor activation (Reddy et al, 2018). Experimental work in vitro in OSNs has suggested the existence of non-linear interactions, especially antagonism (Firestein and Shepherd, 1992;Kurahashi et al, 1994;Mathis et al, 2016;Rospars et al, 2008Rospars et al, , 2000Singh et al, 2019) (also bioRxiv preprints; Inagaki et al, 2019;Pfister et al, 2019;Xu et al, 2019). However, the prevalence of these interactions, especially in living animals within the constraints of natural sniffing dynamics, has not been explored.…”

Widespread Receptor Driven Modulation in Peripheral Olfactory Coding

“…Inhibition or antagonism has been previously observed for single receptor neurons tested with monomolecular compounds 8,[18][19][20][21][22][23] . Moreover, multiple mathematical and biophysical models have been proposed to describe the consequences of mixing two odors that included suppression and/or inhibition 21,[35][36][37] . However, the low throughput of classical methods to assess cell-specific responses to multiple odors has made it very difficult to quantify the incidence of inhibition in practice and therefore tis relevance to perception.…”