Olfactory receptor antagonism between odorants

The detection of thousands of volatile odorants is mediated by several hundreds of different G protein-coupled olfactory receptors (ORs). The main strategy in encoding odorant identities is a combinatorial receptor code scheme in that different odorants are recognized by different sets of ORs. Despite increasing information on agonist-OR combinations, little is known about the antagonism of ORs in the mammalian olfactory system. Here we show that odorants inhibit odorant responses of OR(s), evidence of antagonism between odorants at the receptor level. The antagonism was demonstrated in a heterologous OR-expression system and in single olfactory neurons that expressed a given OR, and was also visualized at the level of the olfactory epithelium. Dual functions of odorants as an agonist and an antagonist to ORs indicate a new aspect in the receptor code determination for odorant mixtures that often give rise to novel perceptual qualities that are not present in each component. The current study also provides insight into strategies to modulate perceived odorant quality.     

Comparison of odorant specificity of two human olfactory receptors from different phylogenetic classes and evidence for antagonism

Humans are able to detect and discriminate myriads of odorants using only several hundred olfactory receptors (ORs) classified in two major phylogenetic classes representing ORs from aquatic (class I) and terrestrial animals (class II). Olfactory perception results in a combinatorial code, in which one OR recognizes multiple odorants and different odorants are recognized by different combinations of ORs. Moreover, recent data suggest that odorants could also behave as antagonists for other ORs, thus making the combinatorial coding more complex. Here we describe the odorant repertoires of two human ORs belonging to class I and class II, respectively. For this purpose, we set up an assay based on calcium imaging in which 100 odorants were screened using air-phase odorant stimulation at physiological doses. We showed that the human class I OR52D1 is functional, exhibiting a narrow repertoire related to that of its orthologous murine OR, demonstrating than this human class I OR is not an evolutionary relic. The class II OR1G1 was revealed to be broadly tuned towards odorants of 9-10 carbon chain length, with diverse functional groups. The existence of antagonist odorants for the class II OR was also demonstrated. They are structurally related to the agonists, with shorter carbon chain length.     

Perceptual blending in odor mixtures depends on the nature of odorants and human olfactory expertise

Our olfactory system is confronted with complex mixtures of odorants, often recognized as single entities due to odor blending (e.g., coffee). In contrast, we are also able to discriminate odors from complex mixtures (e.g., off-odors). Therefore, the olfactory system is able to engage either configural or elemental processes when confronted with mixtures. However, the rules that govern the involvement of these processes during odor perception remain poorly understood. In our first experiment, we examined whether simple odorant mixtures (binary/ternary) could elicit configural perception. Twenty untrained subjects were asked to evaluate the odor typicality of mixtures and their constituents. The results revealed a significant increase in odor typicality in some but not all mixtures as compared with the single components, which suggest that perceptual odor blending can occur only in specific mixtures (configural processing). In our second experiment, we tested the hypothesis that general olfactory expertise can improve elemental perception of mixtures. Thirty-two trained subjects evaluated the odor typicality of the stimuli presented during the first experiment, and their responses were compared with those obtained from the untrained panelists. The results support the idea that general training with odors increases the elemental perception of binary and ternary blending mixtures.     

Different thresholds for detection and discrimination of odors in the honey bee (Apis mellifera)

Naturally occurring odors used by animals for mate recognition, food identification and other purposes must be detected at concentrations that vary across several orders of magnitude. Olfactory systems must therefore have the capacity to represent odors over a large range of concentrations regardless of dramatic changes in the salience, or perceived intensity, of a stimulus. The stability of the representation of an odor relative to other odors across concentration has not been extensively evaluated. We tested the ability of honey bees to discriminate pure odorants across a range of concentrations at and above their detection threshold. Our study showed that pure odorant compounds became progressively easier for honey bees to discriminate with increasing concentration. Discrimination is, therefore, a function of odorant concentration. We hypothesize that the recruitment of sensory cell populations across a range of concentrations may be important for odor coding, perhaps by changing its perceptual qualities or by increasing its salience against background stimuli, and that this mechanism is a general property of olfactory systems.     

Just noticeable differences in component concentrations modify the odor quality of a blending mixture

The odors we perceive are mainly the result of mixtures of odorants that, however, are commonly perceived as single undivided entities; nevertheless, the processes involved remain poorly explored. It has been recently reported that perceptual blending based on configural olfactory processing can cause odorant mixtures to give rise to an emergent odor not present in the components. The present study examined whether specific component proportions are required to elicit an emergent odor. Starting from the composition of a ternary target mixture in which an emergent pineapple odor was perceived, 4 concentration levels of each component were chosen to elicit just noticeable differences (JNDs). Each combination of levels was used to design sample mixtures. Fifteen subjects evaluated the intensity, typicality, and pleasantness of each sample mixture against the target mixture in a paired-comparison protocol. Statistical modeling showed that a variation of less than 1 JND in one of the components was sufficient to induce a significant decrease in pineapple odor typicality in the ternary mixture. This finding confirms previous findings on perceptual blending in simple odorant mixtures and underscores the human ability to discriminate between odor percepts induced by mixtures including very similar odorant proportions.     

Molecular and cellular basis of human olfaction

The human olfactory systems recognize and discriminate a large number of different odorant molecules. The detection of chemically distinct odorants begins with the binding of an odorant ligand to a specific receptor protein in the ciliary membrane of olfactory neurons. To address the problem of olfactory perception at a molecular level, we have cloned, functionally expressed, and characterized some of the human olfactory receptors from chromosome 17. Our results show that a receptor protein is capable of recognizing the particular chemical substructure of an odor molecule and, therefore, is able to respond only to odorants that have a defined molecular structure. These findings represent the beginning of the molecular understanding of odorant recognition in humans. In the future, this knowledge could be used for the design of synthetic ideal receptors for specific odors (biosensors), or the perfect odor molecule for a given receptor.     

Odor representations in the rat olfactory bulb change smoothly with morphing stimuli

Many species of mammals are very good at categorizing odors. One model for how this is achieved involves the formation of "attractor" states in the olfactory processing pathway, which converge to stable representations for the odor. We analyzed the responses of rat olfactory bulb mitral/tufted (M/T) cells using stimuli "morphing" from one odor to another through intermediate mixtures. We then developed a phenomenological model for the representation of odors and mixtures by M/T cells and show that >80% of odorant responses to different concentrations and mixtures can be expressed in terms of smoothly summing responses to air and the two pure odorants. Furthermore, the model successfully predicts M/T cell responses to odor mixtures when respiration dependence is eliminated. Thus, odor mixtures are represented in the bulb through summation of components, rather than distinct attractor states. We suggest that our olfactory coding model captures many aspects of single and mixed odor representation in M/T cells.     

Olfactory receptor cells respond to odors in a tissue and semiconductor hybrid neuron chip

Olfactory systems of human beings and animals have the abilities to sense and distinguish varieties of odors. In this study, a bioelectronic nose was constructed by fixing biological tissues onto the surface of light-addressable potentiometric sensor (LAPS) to mimic human olfaction and realize odor differentiation. The odorant induced potentials on tissue-semiconductor interface was analyzed by sensory transduction theory and sheet conductor model. The extracellular potentials of the receptor cells in the olfactory epithelium were detected by LAPS. Being stimulated by different odorants, such as acetic acid and butanedione, olfactory epithelium activities were analyzed on basis of local field potentials and presented different firing modes. The signals fired in different odorants could be distinguished into different clusters by principal component analysis (PCA). Therefore, with cellular populations well preserved, the epithelium tissue and LAPS hybrid system will be a promising neuron chip of olfactory biosensors for odor detecting.     

Humans and Mice Express Similar Olfactory Preferences

In humans, the pleasantness of odors is a major contributor to social relationships and food intake. Smells evoke attraction and repulsion responses, reflecting the hedonic value of the odorant. While olfactory preferences are known to be strongly modulated by experience and learning, it has been recently suggested that, in humans, the pleasantness of odors may be partly explained by the physicochemical properties of the odorant molecules themselves. If odor hedonic value is indeed predetermined by odorant structure, then it could be hypothesized that other species will show similar odor preferences to humans. Combining behavioral and psychophysical approaches, we here show that odorants rated as pleasant by humans were also those which, behaviorally, mice investigated longer and human subjects sniffed longer, thereby revealing for the first time a component of olfactory hedonic perception conserved across species. Consistent with this, we further show that odor pleasantness rating in humans and investigation time in mice were both correlated with the physicochemical properties of the molecules, suggesting that olfactory preferences are indeed partly engraved in the physicochemical structure of the odorant. That odor preferences are shared between mammal species and are guided by physicochemical features of odorant stimuli strengthens the view that odor preference is partially predetermined. These findings open up new perspectives for the study of the neural mechanisms of hedonic perception.