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

Abstract Odor landscapes contain complex blends of discrete 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 found widespread antagonistic interactions in binary odor mixtures. In complex mixtures of up to 12 odorants, antagonistic interactions became stronger and more prevalent with increasing mixture complexity. Therefore, antagonism is a remarkably common feature of odor mixture encoding in olfactory sensory neurons and helps in normalizing activity to reduce saturation.