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September 5, 2019Open Access

Odorant Receptor Inhibition is Fundamental to Odor Encoding

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Authors

PPPatrick PfisterFirmenich (United States)BSBenjamin C. SmithFlorida State UniversityBEBarry J. EvansUniversity Hospitals of Derby and Burton NHS Foundation Trust

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Implication

Laboratory study demonstrates widespread odorant receptor antagonism in mouse olfactory sensory neurons, indicating extensive peripheral signal computation before bulb transmission.

Key Points

  • To determine the prevalence, functional consequences, and conservation of odorant receptor antagonism in peripheral olfactory neurons during odor mixture processing.
  • Monitored dissociated olfactory sensory neuron responses to indole and 36 test odorants using calcium imaging microscopy.
  • Identified candidate receptor genes via single-cell transcriptomics on responsive neurons and validated Olfr743 function in vitro.
  • Screened 10 Olfr743 clade receptors against 800 perfumery odorants and evaluated response patterns using a mathematical model of competitive binding.
  • Observed substantial inhibition, including complete attenuation, of indole responses across dissociated olfactory sensory neurons exposed to 36 test odorants.
  • Identified that 430 of 800 screened odorants antagonized at least one of the 10 Olfr743 clade receptors, displaying divergent response profiles even across close paralogs.
  • Demonstrated that receptor responses fit competitive binding kinetics, establishing that mixture normalization via antagonism, inverse agonism, and partial agonism occurs prior to olfactory bulb relay.

Cite This Study

Pfister et al. (2019) studied this question.

synapsesocial.com/papers/6a89828b991508d05dc989f9https://doi.org/10.1101/760033
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