Reconstitution and visualization of odorant responses in olfactory neurons

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The vertebrate olfactory system discriminates a wide variety of odorants by relaying coded information from olfactory sensory neurons in the olfactory epithelium to olfactory cortical areas of the brain. Recent studies have shown that the first step in odor discrimination is mediated by approximately one thousand distinct olfactory receptors, which comprise the largest family of G protein-coupled receptors. In the present study, we used Ca^<2+> imaging techniques to functionally clone and reconstitute structurally-related mouse olfactory receptors that bind overlapping sets of odorants with distinct affinities and specificities. Our results provide direct evidence for the existence of a receptor code in which the identities of different odorants are specified by distinct combinations of odorant receptors that possess unique molecular receptive ranges. We further demonstrate that the receptor code for an odorant changes with odorant concentration. Finally, we show that odorant receptors in HEK293T cells couple to stimulatory G proteins such as Gαolf, resulting in odorant-dependent increases in cAMP.Odor discrimination is thus determined by differences in the receptive ranges of the odorant receptors that together encode specific odorant molecules.