Modulation of the combinatorial code of odorant receptor response patterns in odorant mixtures

Claire A. de March, William B. Titlow, Tomoko Sengoku, Patrick Breheny, Hiroaki Matsunami, Timothy S. McClintock

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


The perception of odors relies on combinatorial codes consisting of odorant receptor (OR) response patterns to encode odor identity. Modulation of these patterns by odorant interactions at ORs potentially explains several olfactory phenomena: mixture suppression, unpredictable sensory outcomes, and the perception of odorant mixtures as unique objects. We determined OR response patterns to 4 odorants and 3 binary mixtures in vivo in mice, identifying 30 responsive ORs. These patterns typically had a few strongly responsive ORs and a greater number of weakly responsive ORs. ORs responsive to an odorant were often unrelated sequences distributed across several OR subfamilies. Mixture responses predicted pharmacological interactions between odorants, which were tested in vitro by heterologous expression of ORs in cultured cells, providing independent evidence confirming odorant agonists for 13 ORs and identifying both suppressive and additive effects. This included 11 instances of antagonism of ORs by an odorant, 1 instance of additive responses to a binary mixture, 1 instance of suppression of a strong agonist by a weak agonist, and the discovery of an inverse agonist for an OR. Interactions between odorants at ORs are common even when the odorants are not known to interact perceptually in humans, and in some cases interactions at mouse ORs correlate with the ability of humans to perceive an odorant in a mixture.

Original languageEnglish
Article number103469
JournalMolecular and Cellular Neuroscience
StatePublished - Apr 2020

Bibliographical note

Funding Information:
We thank Dr. Ken Campbell, Dr. Michael Renfro and Mr. Herb Mefford for technical assistance. This work was supported by grants from the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health of the United States of America, R01DC014423 to H.M. and R01DC014468 to T.S.M.

Publisher Copyright:
© 2020 Elsevier Inc.


  • G protein-coupled receptors
  • Olfaction
  • Olfactory coding
  • Olfactory sensory neurons

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology


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