Supersensitive detection and discrimination of enantiomers by dorsal olfactory receptors: evidence for hierarchical odour coding.

Takaaki Sato,Ko Kobayakawa,Akio Tsuboi,Miwako Kizumi,Makoto Emura,Shigeyoshi Itohara,Hiroshi Hamana,Reiko Kobayakawa,Junzo Hirono

doi:10.1038/srep14073

Abstract

Enantiomeric pairs of mirror-image molecular structures are difficult to resolve by instrumental analyses. The human olfactory system, however, discriminates (−)-wine lactone from its (+)-form rapidly within seconds. To gain insight into receptor coding of enantiomers, we compared behavioural detection and discrimination thresholds of wild-type mice with those of ΔD mice in which all dorsal olfactory receptors are genetically ablated. Surprisingly, wild-type mice displayed an exquisite “supersensitivity” to enantiomeric pairs of wine lactones and carvones. They were capable of supersensitive discrimination of enantiomers, consistent with their high detection sensitivity. In contrast, ΔD mice showed selective major loss of sensitivity to the (+)-enantiomers. The resulting 108-fold differential sensitivity of ΔD mice to (−)- vs. (+)-wine lactone matched that observed in humans. This suggests that humans lack highly sensitive orthologous dorsal receptors for the (+)-enantiomer, similarly to ΔD mice. Moreover, ΔD mice showed >1010-fold reductions in enantiomer discrimination sensitivity compared to wild-type mice. ΔD mice detected one or both of the (−)- and (+)-enantiomers over a wide concentration range, but were unable to discriminate them. This “enantiomer odour discrimination paradox” indicates that the most sensitive dorsal receptors play a critical role in hierarchical odour coding for enantiomer identification.

Highlights

The high overlap at higher odourant concentrations suggested that a minority of the most sensitive receptors plays a key role in determining odour quality differences between enantiomers and enabling their discrimination
Detection threshold was defined as the lowest concentration of odourant solution for which the average correct odour choice rate (COCR) for the target odour was significantly higher than chance (> 59.43%, P < 0.05 for 108 trials; χ 2-test, Supplementary Information Table ST1)
We focused on comparing threshold concentrations, where only the most sensitive olfactory receptors (ORs) would be activated

Summary

Introduction

The high overlap at higher odourant concentrations suggested that a minority of the most sensitive receptors plays a key role in determining odour quality differences between enantiomers and enabling their discrimination This led us to formulate a model of odour quality coding in which signals transduced by cognate receptors and relayed as inputs through segregated channels in the olfactory bulb[11,12,13], are processed in the olfactory cortex to evoke ‘elemental’ perceived odour qualities. Three distinct subsets of murine ORs completely matched human odour percepts of vanilla, creamy and cinnamon, respectively We extended these findings by showing similarities of enantiomer odour detection sensitivity difference across humans and Δ D mice. Our comparison of behavioural discrimination thresholds with detection thresholds in WT and Δ D mice indicates that the most sensitive dorsal receptors play a critical role in hierarchical odour coding for enantiomer identification

Methods

Results

Conclusion