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

Joseph D Zak,Gautam Reddy,Massimo Vergassola,Venkatesh N Murthy

doi:10.1038/s41467-020-17124-5

Abstract

Odor landscapes contain complex blends of molecules that each activate unique, overlapping populations of olfactory sensory neurons (OSNs). Despite the presence of hundreds of OSN subtypes in many animals, the overlapping nature of odor inputs may lead to saturation of neural responses at the early stages of stimulus encoding. Information loss due to saturation could be mitigated by normalizing mechanisms such as antagonism at the level of receptor-ligand interactions, whose existence and prevalence remains uncertain. By imaging OSN axon terminals in olfactory bulb glomeruli as well as OSN cell bodies within the olfactory epithelium in freely breathing mice, we find widespread antagonistic interactions in binary odor mixtures. In complex mixtures of up to 12 odorants, antagonistic interactions are stronger and more prevalent with increasing mixture complexity. Therefore, antagonism is a common feature of odor mixture encoding in OSNs and helps in normalizing activity to reduce saturation and increase information transfer.

Highlights

Odor landscapes contain complex blends of molecules that each activate unique, overlapping populations of olfactory sensory neurons (OSNs)
Recent theoretical work has shown that a variety of nonlinear interactions among multiple ligands at the same receptor can readily arise with a simple two-step model of receptor activation[11] (Fig. 1b, c)
Odor responses in OSNs can be measured with excellent sensitivity in the glomerular layer of the olfactory bulb, where axons of a given receptor type converge, allowing signal averaging

Summary

Introduction

Odor landscapes contain complex blends of molecules that each activate unique, overlapping populations of olfactory sensory neurons (OSNs). 1234567890():,; The number of distinct types of sensory neurons is usually far smaller than the number of distinct stimuli that an animal needs to detect, necessitating individual neurons to be receptive to multiple stimuli This feature is especially relevant in the olfactory system where the number of odorous molecules vastly exceeds the repertoire of receptor types[1,2,3]. By delivering odors individually and in binary mixtures at concentrations that varied over three orders of magnitude, we uncover evidence for multistep activation of ORs and for widespread antagonistic interactions We find such antagonistic interactions in responses to complex mixtures containing up to 12 components in single OSNs. Our data strongly support a role for mixture suppression of OSN activity as a normalizing mechanism in olfactory stimulus encoding, which could enhance odor information transfer

Methods

Results

Conclusion