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Perception of the wide, complex and changing odour environment requires that the olfactory system engages processing mechanisms ensuring efficient detection and discrimination of stimuli ending in specific motor actions and in adaptation. In newborn rabbits detecting and responding to the mammary pheromone (MP) emitted by the mother is crucial for survival, since the MP is a strong releaser of typical head-searching/oral grasping behaviour allowing to locate and orally grasp the maternal nipples during the daily nursing. Strikingly, the MP also functions as a natural reinforcer, i.e. as an unconditioned stimulus able to promote appetitive conditioning to a new odorant (CS) in a single and very brief (5 min) association. We have already shown that such MP-induced odour learning, which involves peripheral plasticity (induction) and cerebral plasticity, results in an increase in detection threshold of the CS. These results were obtained when the CS was used at a single concentration (10-5 g/ml). Here, we investigated whether and how the use of a CS (ethyl isobutyrate) at different concentrations (from 10-5 to 10-23 g/ml) during pairing with the MP, influences post-conditioning detection threshold of the CS. The results highlight that the lower the CS concentration, the lower the detection threshold. However, below a certain concentration level, the response range no longer includes the highest CS concentrations but shifts and focuses around the conditioning concentration. These results are original both because they pinpoint 1) detection capability of a learned odorant at exceptionally low concentrations, and 2) that for low concentrations, the perceived quality of the CS is altered. The study provides a novel insight into olfactory perceptual sensitivity in neonates, as well as evidence of discontinuity in perceived odorant quality at very low intensity.

Odorants are relatively small molecules which are easily taken up and distributed in the human body. Despite their relevance in everyday life, however, only a limited amount of evidence about their metabolism, pathways, and bioactivities in the human body exists. With this Review, we aim to encourage future interdisciplinary research on the function and mechanisms of the biotransformation of odorants, involving different disciplines such as nutrition, medicine, biochemistry, chemistry, and sensory sciences. Starting with a general overview of the different ways of odorant uptake and enzymes involved in the metabolism of odorants, a more precise description of biotransformation processes and their function in the oral cavity, the nose, the lower respiratory tract (LRT), and the gastrointestinal tract (GIT) is given together with an overview of the different routes of odorant excretion. Finally, perspectives for future research are discussed.

Flavor is the main factor determining food acceptability. Flavor corresponds to the combination of the signals from the gustatory system, the olfactory system and the trigeminal system. Interactions between proteins and flavor molecules in oral/nasal cavities are proposed to modulate flavor perception through a series of events knowns as perireceptor events. Among these proteins involved in this modulation are found enzymes mainly known for their role in the detoxification process. These enzymes are able to recognize a large panel of molecules. We proposed to explore the role of these enzymes in food perception. We demonstrated that enzymatic activities present in the oral epithelium and saliva, and in the olfactory mucus led to odorant molecules metabolization. Enzymes metabolize odorant molecules in order to eliminate them, consequently participating to the termination of the flavor signal. Additionally, the odorant metabolites have their own sensory properties and can also be perceived, contributing to modulate the flavor perception. Using a combination of technics including mass spectroscopy, immunohistochemistry, enzymology and radiocristallography, we identify and characterize different enzymes related to this flavor perception in the oral cavity (at the level of aroma molecules and tastants). This research contributes to clarify the understanding of the metabolization of odorant and tastant molecules in the oral cavity and their consequences on flavor perception.

Flavour perception results from the interactions of many molecules in mouth, including the ones that occur between oral enzymes and odorants or tastants, which are released upon food mastication. Taste perception results from the activation of taste receptors present in the taste buds, which are bathed in saliva. As a result, molecules eliciting the taste modality have to be dissolved in saliva to reach the taste receptors and interact with salivary proteins. Some of these salivary proteins have a carrier role or a metabolization role via their enzymatic activity. Among these proteins are found some enzymes involved in the detoxification process. Interestingly, they can potentially recognize a large panel of molecules including taste molecules. The aim of this work was to characterise the presence of such enzymes in saliva, their ability to bind taste compounds and consequently to discuss their possible role in taste modulation.

National audience

International audience; A functional sense of smell is essential for evaluating and enjoying food, receiving information about conspecifics, and detecting threats via airborne chemical cues. Olfactory dysfunction has been associated with an impaired quality of life, reflected by a higher incidence of undesirable mental states such as depression and social insecurity. Addressing and overcoming related olfactory dysfunction issues require a detailed understanding of peripheral and central processes involved in olfaction. Consequently, there is a growing body of research unravelling molecular and cellular interactions that shape olfactory sensation. Recent studies have demonstrated that in the nasal mucosa odorants are biotransformed by metabolizing enzymes into metabolites that themselves have signaling properties. In addition, the demonstration that metabolites synthesis is very fast (hundreds of millisecond range) supports a potential functional impact of these odorous metabolites on olfactory perception. Therefore, an advanced characterization of this hitherto neglected mechanism could radically change our understanding of olfactory perception.The underlying enzymatic processes involved in nasal odorant biotransformation have been investigated for few odorants, to date, and knowledge on the odor characteristics of nasal volatile metabolites is very limited. Here, we present the international consortium “NAOMI” which combines different expertises to explore the formation, the identity, and the sensory properties of volatile odorant metabolites through complementary studies in animal and cellular models, as well as human sensory approaches. The aim is to gain a comprehensive understanding of how aroma and odor perception is shaped by nasal metabolic products. NAOMI brings together multi-disciplinary skills ranging from clinical expertise in Oto-Rhino-Laryngology (Hackenberg) and airway tissue engineering (Steinke), over molecular biology/enzymology (Heydel, Le Quéré, Neiers, Reynaud, Thomas-Danguin) to aroma chemistry and sensory evaluation (Buettner, Kornbausch, Loos, Thomas-Danguin). Comprising both the detailed characterization of molecular processes as well as of sensory correlates, the NAOMI consortium aims to better understand how molecular enzymatic mechanisms shape olfactory perception. This project is supported by ANR and DFG.

International audience; Lingering in the background of every odorant-receptor interaction is an odor metabolizing enzyme. Over the last several years, a fascinating set of studies in rodents, rabbits, insects and humans has demonstrated that these enzymes participate in the active biotransformation of odorous molecules within the perireceptor environment. These mechanisms may exert two unique effects: first, to maintain odor sensitivity by reducing receptor saturation, and second, to transform the local milieu of the odor components giving rise to unique odor percepts. This symposium will focus on the impact of odorant metabolizing enzymes (OMEs) on functional and behavioral aspects of olfactory perceptual processing. Individual presentations will span in vitro, in vivo, and ex vivo models of odor enzymatic biotransformation, and will also span different model systems from insects to rodents to humans. Dr. Andrea Buettner will describe her food chemistry research illustrating the metabolic and perceptual consequences of ingested odors on the generation of new odor volatiles; Dr. Thomas Chertemps will present recent electrophysiological and molecular biology work involving effects of insect OMEs on the perception of pheromones and host odors; Dr. Hiro Matsunami will speak about his latest findings examining how OMEs modulate the activation of odorant receptors in vitro; and Dr. Aline Robert-Hazotte will discuss her newest findings linking effects of peripheral OME activity on human olfactory perception. This symposium will highlight cutting-edge work across different countries (USA, Germany, France) and different levels of training (1 postdoc scholar, 2 full professors, 1 assistant professor), and is evenly balanced across women and men. Together this set of talks will bring innovative and integrative understanding to the role and relevance of OME activity on chemosensory function.

WOS:000529189000001This article belongs to the Special Issue Olfaction: From Genes to Behavior.; International audience; The detection and processing of chemical stimuli involve coordinated neuronal networks that process sensory information. This allows animals, such as the model species Drosophila melanogaster, to detect food sources and to choose a potential mate. In peripheral olfactory tissues, several classes of proteins are acting to modulate the detection of chemosensory signals. This includes odorant-binding proteins together with odorant-degrading enzymes (ODEs). These enzymes, which primarily act to eliminate toxic compounds from the whole organism also modulate chemodetection. ODEs are thought to neutralize the stimulus molecule concurrently to its detection, avoiding receptor saturation thus allowing chemosensory neurons to respond to the next stimulus. Here, we show that one UDP-glycosyltransferase (UGT36E1) expressed in D. melanogaster antennal olfactory sensory neurons (OSNs) is involved in sex pheromone discrimination. UGT36E1 overexpression caused by an insertion mutation affected male behavioral ability to discriminate sex pheromones while it increased OSN electrophysiological activity to male pheromones. Reciprocally, the decreased expression of UGT36E1, controlled by an RNAi transgene, improved male ability to discriminate sex pheromones whereas it decreased electrophysiological activity in the relevant OSNs. When we combined the two genotypes (mutation and RNAi), we restored wild-type-like levels both for the behavioral discrimination and UGT36E1 expression. Taken together, our results strongly suggest that this UGT plays a pivotal role in Drosophila pheromonal detection.