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

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

Author information

1
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.
2
University Program in Genetics and Genomics, Duke University Medical Center, Durham, North Carolina, USA.
3
Department of Statistical Science, Duke University, Durham, North Carolina, USA.
4
Department of Neurobiology, Duke Institute for Brain Sciences, Duke University Medical Center, Durham, North Carolina, USA.

Abstract

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.

PMID:
26322927
PMCID:
PMC4583814
DOI:
10.1038/nn.4104
[Indexed for MEDLINE]
Free PMC Article

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