Widespread Receptor Driven Modulation in Peripheral Olfactory Coding

Abstract

<jats:title>Abstract</jats:title><jats:p>We utilized swept confocally aligned planar excitation (SCAPE) microscopy to measure odor-driven activity simultaneously in many (&gt;10,000) olfactory sensory neurons distributed over large areas of intact mouse olfactory epithelium. This approach allowed us to investigate the responses to mixtures or blends of odors and their components, a more realistic stimulus than monomolecular odors. In up to 38% of responding cells, responses to a mixture of odors were different - absent, smaller or larger - than what would be expected from the sum of the individual components. Further investigation revealed instances of both antagonism and allosteric enhancement in the primary olfactory sensory neurons. All 10 of the odor compounds tested were found to act as both agonists and antagonists at different receptors. We present a hypothetical scheme for how modulation at the peripheral receptors increases the capability of the olfactory system to recognize patterns of complex odor mixtures. The widespread modulation of primary sensory receptors argues against a simple combinatorial code and should motivate a search for alternative coding strategies.</jats:p>

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

“…Beyond our theoretical observations, there are other more recent experimental studies (in bioRxiv preprints) that report related effects (Inagaki et al, 2019;Pfister et al, 2019;Xu et al, 2019). Our work is unique in the following regard:…”

“…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.…”