Perceptual Effects of Odorant Antagonists

Summary/Abstract Dr. McClintock’s research on the function of receptors responsive to odors uses a technology that simultaneously measures the responses of all 1,100 odorant receptors (ORs) and all 14 trace-amine associated receptors (TAARs) to odors in freely behaving mice, capturing the receptor response patterns that encode odors. These patterns, often called combinatorial codes, are responsible for odor identification and discrimination. This technology quantifies both response and loss of response from ORs and TAARs so a major theme of these studies is investigating the role of odorant interactions in shaping response patterns. These interactions are common, and evidence is rapidly accumulating that most interactions are competitive antagonism. Many odorants tested thus far have proven to be both agonists and antagonists, activating some ORs while simultaneously suppressing responses from other ORs. Because odors are nearly always mixtures of many different odorants, these findings predict that odorant interactions are fundamental to the encoding and perception of odors in mammals. While investigating how these interactions affect odor perception is generally important for understanding neural coding, odorant interactions also have translational potential. Prime examples are blocking perception of malodors that have negative impacts on human health and quality of life. These translational opportunities predict are certain to motivate work on the development of pharmacological tools to modify responses from specific ORs and TAARs and thereby manipulate the perception of certain odors. Training in human olfactory psychophysics will put Dr. McClintock in position to leverage his preclinical data on odorant interactions into tests of whether these interactions have translational utility in humans. This application proposes training in working with human subjects, in selecting the appropriate psychophysical test and odor concentrations, in methods for of delivering odors to humans, and in controlling the odor environment experienced by humans during testing.