Journal Article

Antagonism in olfactory receptor neurons and its implications for the perception of odor mixtures

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

2018

Overview

Natural environments feature mixtures of odorants of diverse quantities, qualities and complexities. Olfactory receptor neurons (ORNs) are the first layer in the sensory pathway and transmit the olfactory signal to higher regions of the brain. Yet, the response of ORNs to mixtures is strongly non-additive, and exhibits antagonistic interactions among odorants. Here, we model the processing of mixtures by mammalian ORNs, focusing on the role of inhibitory mechanisms. We show how antagonism leads to an effective ‘normalization’ of the ensemble ORN response, that is, the distribution of responses of the ORN population induced by any mixture is largely independent of the number of components in the mixture. This property arises from a novel mechanism involving the distinct statistical properties of receptor binding and activation, without any recurrent neuronal circuitry. Normalization allows our encoding model to outperform non-interacting models in odor discrimination tasks, leads to experimentally testable predictions and explains several psychophysical experiments in humans. When ordering in a coffee shop, you probably recognize and enjoy the aroma of freshly roasted coffee beans. But as well as coffee, you can also smell the croissants behind the counter and maybe even the perfume or cologne of the person next to you. Each of these scents consists of a collection of chemicals, or odorants. To distinguish between the aroma of coffee and that of croissants, your brain must group the odorants appropriately and then keep the groups separate from each other. This is not a trivial task. Odorants bind to proteins called odorant receptors found on the surface of cells in the nose called olfactory receptor neurons. But each odorant does not have its own dedicated receptor. Instead, a single odorant will bind to multiple types of odorant receptors, and thus, each olfactory receptor neuron may respond to multiple odorants. So how does the brain encode mixtures of odorants in a way that allows us to distinguish one aroma from another? Reddy, Zak et al. have developed a computational model to explain how this process works. The model assumes that an odorant triggers a response in an olfactory receptor neuron via two steps. First, the odorant binds to an odorant receptor. Second, the bound odorant activates the receptor. But the odorant that binds most strongly to a receptor will not necessarily be the odorant that is best at activating that receptor. This allows a phenomenon called competitive antagonism to occur. This is when one odorant in a mixture binds more strongly to a receptor than the other odorants, but only weakly activates that receptor. In so doing, the strongly bound odorant prevents the other odorants from binding to and activating the receptor. This helps tame the dominating influence of background odors, which might otherwise saturate the responses of individual olfactory receptor neurons. Reddy, Zak et al. show that processes such as competitive antagonism enable olfactory receptor neurons to encode all of the odors within a mixture. The model can explain various phenomena observed in experiments and it adds to our understanding of how the brain generates our sense of smell. The model may also be relevant to other biological systems that must filter weak signals from a dominant background. These include the immune system, which must distinguish a small set of foreign proteins from the much larger number of proteins that make up our bodies.

• Publisher: eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Action Potentials / Aroma compounds / Computational and Systems Biology / decoding / encoding / Humans / Ligands / mixture interaction / Models, Neurological / Neuroscience / normalization / odor perception / Odorant receptors / Odorants / Odors / Olfactory discrimination / Olfactory discrimination learning / Olfactory Perception / Olfactory receptor neurons / Olfactory Receptor Neurons - metabolism / Psychophysics / Ratios / Sensory evaluation / Signal transduction / Smell - physiology