Molecular profiling of activated olfactory neurons identifies odorant receptors for odors in vivo

Nat Neurosci. 2015 Oct;18(10):1446-54. doi: 10.1038/nn.4104. Epub 2015 Aug 31.


The mammalian olfactory system uses a large family of odorant receptors (ORs) to detect and discriminate amongst a myriad of volatile odor molecules. Understanding odor coding requires comprehensive mapping between ORs and corresponding odors. We developed a means of high-throughput in vivo identification of OR repertoires responding to odorants using phosphorylated ribosome immunoprecipitation of mRNA from olfactory epithelium of odor-stimulated mice followed by RNA-Seq. This approach screened the endogenously expressed ORs against an odor in one set of experiments using awake and freely behaving mice. In combination with validations in a heterologous system, we identified sets of ORs for two odorants, acetophenone and 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), encompassing 69 OR-odorant pairs. We also identified shared amino acid residues specific to the acetophenone or TMT receptors and developed models to predict receptor activation by acetophenone. Our results provide a method for understanding the combinatorial coding of odors in vivo.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Female
  • Gene Expression Profiling / methods
  • High-Throughput Nucleotide Sequencing
  • Immunohistochemistry
  • In Situ Hybridization
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurons / metabolism*
  • Olfactory Receptor Neurons / metabolism*
  • Polymerase Chain Reaction
  • Receptors, Odorant / metabolism*
  • Smell / physiology


  • Receptors, Odorant

Associated data

  • GEO/GSE59324