Perceptual Effects of Odorant Antagonists

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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 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. Whether these interactions at receptors correctly predict perceptual effects, especially in humans, is as yet unknown so studies of perceptual effects represent a way to assess mechanistic commonality with humans. Investigating how these interactions affect odor perception is generally important for understanding neural coding and antagonist interactions are valuable tools for future studies of odor signal processing in the brain. In addition, 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 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 proposed in this application will put Dr. McClintock in position to leverage his preclinical data on odorant interactions into tests of whether these interactions are mechanisms shared with humans and whether certain odorant interactions have translational utility in humans.