Single olfactory receptors set odor detection thresholds

Abstract

Menzie for technical support, and William Kath and Rosemary Braun for statistical advice. We acknowledge Lynn Doglio and the Transgenesis and Targeted Mutagenesis Laboratory at Northwestern University for transgenic mouse production. Contributions A.D. and T.B conceived the project. A.D., D.R. and T.B. designed the experiments and the behavioral setups. A.D. performed all behavioral experiments and data analysis. A.C. performed in vivo imaging experiments and analysis. J.Z. performed electrophysiological recordings and analysis. K.M performed DREAM experiments and analysis. P.F. conceived the transgenic strategy and helped generate the receptor overexpressing mice. A.D. and T.B. wrote the manuscript with input from all authors. The authors declare no competing interests. 2 ABSTRACTIn many species, survival depends on olfaction, yet the mechanisms that underlie olfactory sensitivity are not well understood. Here, we examine how a conserved subset of olfactory receptors, the trace amine-associated receptors (TAARs) determine odor detection thresholds of mice to amines. We find that deleting all TAARs, or even single TAARs, results in significant odor detection deficits. This finding is not limited to TAARs, as the deletion of a canonical odorant receptor reduced behavioral sensitivity to its preferred ligand. Remarkably, behavioral threshold is set solely by the most sensitive receptor, with no contribution from other highly sensitive receptors. In addition, increasing the number of sensory neurons (and glomeruli) expressing a threshold-determining TAAR does not improve detection, indicating that sensitivity is not limited by the typical complement of sensory neurons. Our findings demonstrate that olfactory thresholds are set by the single highest affinity receptor, and suggest that TAARs are evolutionarily conserved because they determine the sensitivity to a class of biologically relevant chemicals.

Acquisition of innate odor preference depends on spontaneous and experiential activities during critical period

“…Kir2.1-off mice and PEA-exposed mice could detect PEA at 10 -13 M and 10 -12 M, respectively (Figure 4figure supplement C-D). These thresholds were comparable with those exhibited by the control mice and were consistent with previously reported values (Dewan et al, 2018).…”

“…The Taar5 gene, encoding a receptor for TMA, did not have an obvious change. The down-regulation of Taar4 by PEA exposure was consistent with a previous study (Dewan et al, 2018).…”

Predicting Human Olfactory Perception from Activities of Odorant Receptors

“…One possibility is that only one or few receptors of the many that detect an odorant actually convey percept. The evolutionary landscape should accordingly be coupled to biologically relevant or frequently encountered features of the chemical space, as has been implied by characterizations of receptors highly tuned for musk and onion-related compounds (Ahmed et al, 2018;Noe et al, 2017), in addition to the highly conserved trace amine-associated receptors (TAARs) and their importance in modulating behavioral output in mice (Dewan et al, 2018). In our analyses, the OR specialized for musk was not a top candidate for musk predictions but contributed strongly to predictions of ''sweaty.''…”