Sensitivity-dependent Hierarchical Receptor Codes for Odors

Abstract

In order to comprehend the strategy of odor encoding by odorant receptors, we isolated 2740 mouse receptor neurons from four olfactory epithelial zones and classified them in terms of their sensitivities and tuning specificities to a chiral pair of odorants, S(+)-carvone (caraway-like odor) and R(-)-carvone (spearmint-like odor). Our approach revealed that the majority of receptors at the lowest effective stimulus concentration represented the principal odor qualities characteristic of each enantiomer by means of the principal odor qualities of the odorants for which the receptors were most sensitive. The chiral-non-discriminating receptors were newly recruited 3.7 times of R(-)-carvone-sensitive receptors and totally became 2.8 times (39/14) of R(-)carvone-sensitive receptors in the subpopulations when the stimulus concentration was increased 10-fold [corrected]. More than 80% of the responsive receptors (an estimated 70 +/- alpha types) exhibited overlapping sensitivities between the enantiomers. The signals from the non-discriminating receptors may be reduced to decode the characteristic odor identity for R(-)-carvone in the brain over an adequate range of stimulus strengths. The information processing of odors appears to involve the selective weighting of the signals from the most sensitive receptors. An analysis of the overall receptor codes to carvones indicated that the system employs hierarchical receptor codes: principal odor qualities are encoded by the most sensitive receptors and lower-ranked odor qualities by less sensitive receptors.

Identification of Specific Ligands for Orphan Olfactory Receptors

“…1) and others 4 have observed that some OR, when expressed in HEK-293 cells to- OSN (3). In contrast, in HeLa/15 cells, octanoic acid outperformed nonanedioic and was as good an agonist as nonanoic acid for Ors6 and Ors86, respectively ( Fig.…”

“…A multitude of up to 1000 OR 1 (1,2) and their combinatorial odorant recognition properties (3,4) have made it difficult to assign ligand profiles to individual OR (5). Few studies have associated single odorants with individual OR by means of adenoviral overexpression assays in vivo (6), single-cell RT-PCR of odorant-responsive OSN (3,4,7), and OR gene targeting followed by functional analysis of a single OSN (8).…”

“…Few studies have associated single odorants with individual OR by means of adenoviral overexpression assays in vivo (6), single-cell RT-PCR of odorant-responsive OSN (3,4,7), and OR gene targeting followed by functional analysis of a single OSN (8). The heterologous expression and functional imaging of some Nterminally tagged recombinant OR in HEK-293 cells have been achieved by forcing them to activate phosphoinositol signaling and Ca 2ϩ release via G protein subunits ␣15,16 (7, 9 -11) or other Ca 2ϩ release-activating G proteins (12).…”

Heterologous functional expression system for odorant receptors

“…In mice, approximately 1000 different odorant receptors (ORs), which belong to G-protein-coupled receptors (GPCRs), discriminate and detect a subset of odorants in the respective olfactory sensory neurons (OSNs) (Buck and Axel, 1991;Sato et al, 1994;Malnic et al, 1999;Mori et al, 1999;Touhara et al, 1999;Zhang and Firestein, 2002;Hamana et al, 2003;Araneda et al, 2004). To elucidate the molecular basis of odor discrimination mechanism, it is necessary to determine the odorant specificity of each OR; it is examined by determining the structure-activity relationship (SAR) of various ligands for a target OR.…”

“…Subsequently, the receptor potential causes a transient Ca 2+ increase via Ca 2+ influx through voltage-dependent Ca 2+ channels (Sato et al, 1991;Sato, 1994;Zufall et al, 2000). Because OSNs endogenously contain all the signal cascade components required for signal amplifications and cause a transient increase in Ca 2+ levels, isolated OSNs are ideal for measuring relative sensitivities of a particular OR by Ca-imaging (Hirono et al, 1992;Sato et al, 1994;Malnic et al, 1999;Touhara et al, 1999;Hamana et al, 2003). However, isolated OSNs show a gradual decrease in odor responsiveness, because of apoptosis induction due to cutting the axons during isolation (Carson et al, 2005).…”