Sensitivity-dependent hierarchical receptor codes for odors

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.     

Context-dependent changes in the perception of odor quality

Ambiguous odor compounds, partly citrus-like and partly woodyin odor character, were seen to change in odor quality whenevaluated in the same session as more prototypical odors. Whentested with characteristically citrus odors, the ambiguous compoundsseemed more woody, and when tested with characteristically woodyodors, the ambiguous odorants were higher in citrus character,an example of perceptual contrast. Response frequency biaseswere ruled out as an explanation for this shift by an experimentin which responses other than citrus and woody ratings wereasked of the subjects during the contextual exposure. Simplesensory adaptation was found to be a potential contributor tothe effect, and a sufficient condition to produce similar shiftsin odor quality. However, adaptation was not a necessary conditionto produce the effect. This was seen in reversed pair experimentsin which the contextual odors were presented after the ambiguousstimuli. The contextual shift was robust—it was obtainedwith different ambiguous odors, contextual (conditioning) odors,numbers of contextual odors, orders of presentation of contextualodors relative to ambiguous odors, scale types, and rating tasksduring the presentation of contextual odors.     

Response accuracy and odor sampling time in mice trained to discriminate between enantiomers of carvone and those of terpinen-4-ol

Response accuracy and odor-sampling times were used to compare the ability of mice to detect (+)-carvone and (+)-terpinen-4-ol and to discriminate between enantiomers of carvone and of terpinen-4-ol. Except for increased odor sampling when mice were first exposed to the (+)-carvone odor, there was no difference in odor-sampling time or response accuracy in tests of odor detection or in discriminating between enantiomers of these odorants. These results fail to support the suggestion that odorants that produce different patterns of olfactory bulb activation should be easier to discriminate than those that produce much more similar patterns of bulbar activation.     

Ontogeny of Ultrasonic and Locomotor Responses to Nest Odors in Rodents

SYNOPSIS. Rodents discriminate and prefer familiar odors earlyin life. Almost from birth young rats suckle in response tomaternal odor, but suckle less when nipples are cleaned withorganic solvents. In two-choice tests, young prefer familiarnest odors, whether naturally occurring or artificially presented,and can even be made to tolerate odors normally aversive orto avoid odors normally pleasant. Variations in maternal dietcan alter odor preferences of theyoung. Nest odors can affect vocalization of young rodents. In contrastto the consistent effects of cold temperature and handling inthe many rodents studied, nest odors may affect vocalizationdifferently in different species. For example, familiar odorsreduce calling in rats, but increase calling in pine voles.Nest odor also alters spontaneous activity in young rats, whichlocomoteless when maternal odor is present. In this paper I report that home nest odors enhanced locomotionin rodents of three species (pine voles, Microtus pinetorum;white-footed mice, Peromyscus leucopus; and wild house mice,Mus musculus), but that the age at which this pattern occurredand the relationships of nest odors to vocalizations differedamong the species.     

Specialized receptor neurons for pheromones and host plant odors in the boll weevil, Anthonomus grandis Boh. (Coleoptera: Curculionidae)

Antennal olfactory receptor neurons in the boll weevil, Anthonomusgrandis, were investigated through single neuron recordings.Receptor neurons for both pheromone components and host plantodors were associated with type I sensilla within the sensoryband regions. Nine types of receptor neurons were identified,based on their responsiveness to the four aggregation pheromonecomponents and selected host plant odors. Three receptor neurontypes responded to either compound I, II or IV of the aggregationpheromone. Dose—response curves were similar for eachof these receptor neuron types, which differed only in theirkey compound. In each instance, I neurons responded primarilyto (+)-I, the optical isomer produced by the boll weevil whichwas found to be active in field tests. Receptor neurons forII also responded to a lesser degree to III, its aldehydic analog,at the same stimulus load. Six additional receptor neuron typesresponded to selected host plant odors: ß-caryophyllene,trans-2-hexen-l-o1 and other six carbon alcohols and aldehydes,trans-ß-ocimene, benzaldehyde, linalool, and B-bisabolol.These neurons were as responsive as, or in some cases more responsiveat the same stimulus load as receptor neurons for pheromonecomponents. Receptor neurons responsive to six-carbon alcoholsand aldehydes were generally most responsive to trans-2-hexen-l-ol.Receptor neurons for other plant odors responded principallyto only one compound among the odorants tested. However, responsesof these neurons were not uniform, suggesting possible specializationfor other unidentified key odorants. Comparisons were also madebetween single neuron and electroantennogram responses. Theresults indicate that the boll weevil, a narrowly oligaphagousinsect, detects its host plant at some distance, and utilizesinformation about a wide range of chemical structures in itsolfactory-mediated behavior.     

Judgement of odor intensity is influenced by subjects' knowledge of the odor source

Odor perception, including intensity, is affected by knowledge of odor source. For 76 subjects tested with 24 everyday odorants, ratings of intensity, pleasantness and familiarity were enhanced when subjects either could identify the odor source themselves or were provided with the name by the experimenter. Ratings were highest when subjects judged that the names provided matched their own perception, suggesting an interaction between individuals' cognitive representation of odors and their immediate perceptual experience.     

Recent Results in the Search for New Molecules with Ambergris Odor

The synthesis of new odorant molecules is still a challenging task for the fragrance chemist, because now as ever it is difficult to predict the odor properties of small organic molecules. Therefore, certain tools, such as, e.g., lead‐structure optimization of existing odorants, are helpful techniques. In this article, we describe the synthesis and the odor properties of a new molecule derived by the so‐called ‘seco’ lead‐structure optimization of the ambergris compound Ambroxide^®. Based on these results, more representatives with similar structures have been synthesized and evaluated for their olfactory properties.     

Semantic, typicality and odor representation: a cross-cultural study

This study investigated odor-category organization in threecultures by evaluating (i) the relationship between linguisticand perceptual categorization and (ii) the existence of an internalstructure of odor categories. In the first experiment, threegroups of 30 participants from American, French and Vietnamesecultures performed a sorting task. The first group sorted 40odorants on the basis of odor similarity, the second group sorted40 odor names on the basis of name similarity and the last groupsorted 40 odor names on the basis of imagined odor similarity.Results showed that odor categorization was based on perceptualor conceptual similarity and was in part independent of wordand imagined categorizations. In the second experiment, anothergroup of 30 participants from each culture rated the typicalityof the odorants for 11 odor categories. Results showed thatsome odorants were rated as more typical than others. Moreover,the typicality gradient predicted the odor space obtained inthe odor sorting task in a consensual way among the three cultures.These results suggest that, as for other categories, odor categoriesare based on perceptual similarities rather than on semanticcues. Moreover odor-category structure might have a core representationwhich might be common to different cultures with boundarieswhich might be more culturally dependent.     

Membrane fluidity changes of liposomes in response to various odorants. Complexity of membrane composition and variety of adsorption sites for odorants.

Three kinds of liposomes prepared from phosphatidylcholine (PC), azolectin, and azolectin-containing membrane proteins of the canine erythrocytes were used as models for olfactory cells. To explore properties of the adsorption sites of odorants, membrane fluidity changes in response to various odorants were measured with various fluorescence dyes which monitor the fluidity at different depths and different regions of the membranes. (a) Application of various odorants changed the membrane fluidity of azolectin liposomes. The patterns of membrane fluidity changes in response to odorants having a similar odor were similar to each other and those in response to odorants having different odors were different from each other. These results suggested that odorants having a similar odor are adsorbed on a similar site and odorants having different odors are adsorbed on different sites. (b) Such variation of the pattern was not seen in liposomes of a simple composition (PC liposome). (c) In the proteoliposomes whose composition was more complex than that of azolectin liposomes, the patterns of membrane fluidity changes varied among odorants having a similar odor. It was concluded that liposomes of complex membrane composition have the variety of adsorption sites for odorants.     

Combinatorial receptor codes for odors

The discriminatory capacity of the mammalian olfactory system is such that thousands of volatile chemicals are perceived as having distinct odors. Here we used a combination of calcium imaging and single-cell RT-PCR to identify odorant receptors (ORs) for odorants with related structures but varied odors. We found that one OR recognizes multiple odorants and that one odorant is recognized by multiple ORs, but that different odorants are recognized by different combinations of ORs. Thus, the olfactory system uses a combinatorial receptor coding scheme to encode odor identities. Our studies also indicate that slight alterations in an odorant, or a change in its concentration, can change its "code," potentially explaining how such changes can alter perceived odor quality.     

Odor sensitivity to geosmin enantiomers

Enantiomers of the earthy smelling odorant ‘geosmin’(t-1, 10-dimethyl-t-9-decalol) were tested on 52 human subjectsfor odor threshold ratio (+)/(–) variability. Thresholdconcentrations of (+) and (–) and their (+)/(–)ratios appeared to be monomodally distributed. For most subjects,the ratio varied within a predictable narrow range comparableto that found previously for carvone enantiomers and contraryto the large variability found for -ionone enantiomers (Polaket al., 1989). The natural occurring isomer, (–) geosminhad, on average an x11 lower threshold than (+).     

Olfactory discrimination ability of human subjects for ten pairs of enantiomers.

We tested the ability of human subjects to distinguish between enantiomers, i.e. odorants which are identical except for chirality. In a forced-choice triangular test procedure 20 subjects were repeatedly presented with 10 enantiomeric odor pairs and asked to identify the bottle containing the odd stimulus. We found (i) that as a group, the subjects were only able to significantly discriminate the optical isomers of alpha-pinene, carvone and limonene, whereas they failed to distinguish between the (+)- and (-)-forms of menthol, fenchone, rose oxide, camphor, alpha-terpineol, beta-citronellol and 2-butanol; (ii) marked individual differences in discrimination performance, ranging from subjects who were able to significantly discriminate between 6 of the 10 odor pairs to subjects who failed to do so with 9 of the 10 tasks; (iii) that with none of the 10 odor pairs were the antipodes reported to differ significantly in subjective intensity when presented at equal concentrations; and (iv) that error rates were quite stable and did not differ significantly between sessions, and thus, we observed a lack of learning or training effects. Additional tests of the degree of trigeminality and threshold measurements of the optical isomers of alpha-pinene, carvone and limonene suggest that the discriminability of these three enantiomeric odor pairs is indeed due to differences in odor quality. These findings support the assumption that enantioselective molecular odor receptors may only exist for some but not all volatile enantiomers and thus that chiral recognition of odorants may not be a general phenomenon but is restricted to some substances.     

Study of structural and electronic origin of ambergris odor of some compounds

The correlation between structural, stereochemical as well as electronic features and ambergris odor of some tricyclic ethers is established based on quantum chemical calculation method. A definite structural fragment (a “new ambergris triangle”) with certain electronic properties determining the origin of the odor is revealed. The influence of HOMO-LUMO energy gaps and total energies of some ambergris compounds on their odor intensity is investigated.     

Effect of Aging on Hedonic Appreciation of Pleasant and Unpleasant Odors

Does hedonic appreciation evolve differently for pleasant odors and unpleasant odors during normal aging? To answer this question we combined psychophysics and electro-encephalographic recordings in young and old adults. A first study showed that pleasant odorants (but not unpleasant ones) were rated as less pleasant by old adults. A second study validated this decrease in hedonic appreciation for agreeable odors and further showed that smelling these odorants decreased beta event-related synchronization in aged participants. In conclusion, the study offers new insights into the evolution of odor hedonic perception during normal aging, highlighting for the first time a change in processing pleasant odors.     

Separation and absolute configuration of the enantiomers of a degradation product of the new inhalation anesthetic sevoflurane

In a rebreathing anesthesia circuit, the inhaled anesthetic sevoflurane degrades into at least two products, termed "compound A" and "compound B." The enantiomer separation of the chiral compound B (1,1,1,3,3-pentafluoro-2-(fluoromethoxy)-3-methoxypropane ) by capillary gas chromatography (cGC) using heptakis (2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-beta-cyclodextrin as chiral selector was studied. With this cyclodextrin derivative diluted in the polysiloxane PS 86, an unprecedented high separation factor alpha of 4.1 (at 30 degrees C) was found. Consequently, the enantiomers of compound B were isolated by preparative GC and their specific rotations were measured. In addition, their absolute configurations were determined by X-ray crystallography. To collect the X-ray data, single crystals of both enantiomers were grown in situ on the diffractometer. The levorotatory enantiomer B(-) has the R-configuration while the dextrorotatory enantiomer B(+) has the S-configuration. The elution order of the compound B enantiomers on heptakis (2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-beta-cyclodextrin is R before S.     

Enantiomeric effects on excitation-contraction coupling in frog skeletal muscle by a chiral phenoxy carboxylic acid.

Aromatic monocarboxylic acids are known to significantly potentiate the mechanical response of skeletal muscle fibers. In this study we investigated the effects of enantiomers of 2-(4-chlorophenoxy)propionic acid, chemically one of the simplest aromatic monocarboxylic acids with chiral properties, on mechanical threshold and charge movement in frog skeletal muscle. The R(+), but not the S(-), enantiomer lowered rheobase mechanical threshold and shifted charge movement to more negative potentials. The R(+) enantiomer also significantly slowed charge movement kinetics, with pronounced delays of the OFF charge transitions. These effects required high temperature for their production. The stereospecific actions of the R(+) enantiomer are interpreted in terms of a specific interaction of this compound at an anion-sensitive site involved in excitation-contraction coupling, most likely on the dihydropryidine-sensitive voltage sensor in the T-system.     

'Sniffin' Sticks': Olfactory Performance Assessed by the Combined Testing of Odour Identification, Odor Discrimination and Olfactory Threshold

‘Sniffin’ Sticks' is a new test of nasal chemosensoryperformance based on pen-like odor dispensing devices. It comprisesthree tests of olfactory function, namely tests for odor threshold(n-butanol, testing by means of a single staircase), odor discrimination(15 pairs of odorants, triple forced choice) and odor identification(16 common odorants, multiple forced choice from four verbalitems per test odorant). After extensive preliminary investigationsthe tests were applied to a group of 104 healthy volunteers(52 female, 52 male, mean age 49.5 years, range 18–84years) in order to establish test-retest reliability and tocompare them with an established measure of olfactory performance(the Connecticut Chemosensory Clinical Research Center Test,CCCRC). Performance decreased with increasing age of the subjects(     

Olfactory cues modulate facial attractiveness

We report an experiment designed to investigate whether olfactory cues can influence people's judgments of facial attractiveness. Sixteen female participants judged the attractiveness of a series of male faces presented briefly on a computer monitor using a 9-point visual rating scale. While viewing each face, the participants were simultaneously presented with either clean air or else with 1 of 4 odorants (the odor was varied on a trial-by-trial basis) from a custom-built olfactometer. We included 2 pleasant odors (geranium and a male fragrance) and 2 unpleasant odors (rubber and body odor) as confirmed by pilot testing. The results showed that the participants rated the male faces as being significantly less attractive in the presence of an unpleasant odor than when the faces were presented together with a pleasant odor or with clean air (these conditions did not differ significantly). These results demonstrate the cross-modal influence that unpleasant odors can have on people's judgments of facial attractiveness. Interestingly, this pattern of results was unaffected by whether the odors were body relevant (the body odor and the male fragrance) or not (the rubber and geranium odors).     

Computer modeling of information processing mechanisms in the olfactory system. III. Reproduction of psychophysical phenomena by the olfactory bulb model

Psychophysical phenomena typical of olfaction were reproduced using a computer model of olfactory bulb. The procedure of numerical experiments is described. The model reproduces the following phenomena: fusion of odors, strong and weak odors, suppression of weak odors by strong odors, indemnity of odors, changes in odor with time, consecutive olfactory images, sensibilization, consecutive olfactory constrast, and synergims. It was concluded that computer-assisted experimentation in combination with neurophysiological and psychophysical experiments can considerably increase the efficiency of research of odorants and the olfaction process.     

Stereoselective pharmacokinetics of ornidazole after intravenous administration of individual enantiomers and the racemate

The pharmacokinetics of ornidazole (ONZ) were investigated following i.v. administration of racemic mixture and individual enantiomers in beagle dogs. Plasma concentrations of ONZ enantiomers were analyzed by chiral high-performance liquid chromatography (HPLC) on a Chiralcel OB-H column with quantification by UV at 310 nm. Notably, the mean plasma levels of (-)-ONZ were higher in the elimination phase than those of (+)-ONZ. (-)-ONZ also exhibited greater t1/2, MRT, AUC(0-t) and smaller CL, than those of its antipode. The area under the plasma concentration-time curve (AUC(0-t)) of (-)-ONZ was about 1.2 times as high as that of (+)-ONZ. (+)-ONZ total body clearance (CL) was 1.4 times than its optical antipode. When given separately, there were significant differences in the values of AUC(0-infinity) and CL between ONZ enantiomers (P < 0.05), indicating that elimination of (+)-ONZ was more rapid than that of (-)-ONZ. No significant differences were found between the estimates of the pharmacokinetic parameters of (+)-ONZ or (-)-ONZ, obtained following administration as the individual and as a racemic mixture. This study demonstrates that the elimination of ONZ enantiomers is stereoselective and chiral inversion and enantiomer/enantiomer interaction do not occur when the enantiomers are given separately and as racemic mixture.