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Abstract
In mammals, odors are encoded by a combinatorial code determined by the pattern of responses across hundreds of odorant receptors expressed monogenically and monoallelically in olfactory sensory neurons. The compositions of these receptor response patterns are largely unknown and overlap between them has yet to be explored. Activity-dependent reporter gene expression in freely behaving S100a5-tauGFP mice allowed capture of activated olfactory sensory neurons and identified 168 receptors responsive to moderate concentrations of 1 or more of 12 aliphatic (5 to 8 carbons) ketones, alcohols, and carboxylic acids. These 12 response patterns are remarkably different, with only 19% of the receptors responding to more than 1 of these odorants. This distinctiveness corresponds with the ease of discrimination of these odorants and may help maintain perceptual constancy in the face of response pattern variability, such as across odorant concentrations. This set of 168 receptors is not specific to aliphatic odorants but instead has 16% overlap with the receptors responsive to 7 odors tested previously in vivo, consistent with a receptor repertoire evolved to produce combinatorial codes. Aliphatic odorant response pattern similarity depends more upon odorant functional group than carbon chain length but the impact of chain length increases with the number of carbons. The response patterns to these aliphatic odorants are mostly composed of unrelated receptors, except some patterns contain minor subsets of closely related receptors. These findings argue that the major selective forces driving OR evolution are expansion of the odorant receptor gene family and the production of distinct response patterns.
Document Type
Article
Publication Date
2025
Digital Object Identifier (DOI)
https://doi.org/10.1093/chemse/bjaf041
Funding Information
This work was supported by National Institutes of Health (NIH) grants R01DC014468 (TSM), R01DC020353 (HM), and K99DC018333 (CAdM). HM acknowledges support from National Science Foundation grant 2014217. Conflict of interest statement. HM has received royalties from Chemcom, research grants from Givaudan, and consultant fees from Kao.
Repository Citation
de March, Claire A.; Breheny, Patrick; Titlow, William B.; Matsunami, Hiroaki; and McClintock, Timothy S., "Distinct odorant receptor response patterns to aliphatic odorants in freely behaving mice" (2025). Physiology Faculty Publications. 194.
https://uknowledge.uky.edu/physiology_facpub/194
Notes/Citation Information
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