Presentation description

In nature, odors are mixtures of molecules, leading to potentially complex interactions that can occur at the receptor level. One such interaction is antagonism. Odorant-driven antagonism occurs when an odorant receptor is unable to bind with a ligand (agonist) due to the presence of a similar molecule (antagonist) blocking the receptor binding pocket. To more systematically quantify this interaction, our collaborators tested for antagonism in vitro at the receptor level using binary mixtures and found robust evidence for antagonism. However, it is unclear whether antagonism manifests in the circuitry downstream of the odorant receptors to impact odor encoding. The aim of this project, therefore, was to test for evidence of odorant-driven antagonism in vivo at the level of olfactory sensory neurons. Olfactory sensory neurons express odorant receptors and send projections to the olfactory bulb where they synapse with second-order neurons to encode odor information. We imaged odorant-driven responses of olfactory sensory neurons expressing the optical reporter GCaMP8 in the mouse olfactory bulb, utilizing two-photon microscopy. Mice were awake and head-fixed during experiments. Odors were presented with custom olfactometers, and data was analyzed using custom MATLAB software. We found evidence for antagonism in vivo, though this phenomenon does not seem to be as robust in vivo as it is in vitro. This data provides evidence for antagonistic interactions in vivo, which sets up future studies testing how interactions at the receptor level impact downstream odor processing in the olfactory circuit.