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DISCRIMINATION NERVEUSE OLFACTIVE et REPRESENTATION DE L'ODEUR PAR LE SYSTEME OLFACTIF

Abstract : OLFACTORY NERVOUS DISCRIMINATION AND REPRESENTATION OF ODOR BY THE OLFACTORY SYSTEM. by Gilles SICARD In our thesis, we report a set of studies, mostly published and carried out in collaboration, which clarify the functioning of the periphery of the olfactory system and the rules that govern the encoding of the smell. It is the interaction of odorant molecules and olfactory receptor proteins which is responsible for the activation of olfactory receptor neurons. According to recent literature, the genomic repertoire of olfactory receptors would be vast, of the order of 1000 units in rats, several hundred in amphibians. Some researchers assume that there is only one type of receptor expressed by olfactory receptor neuron. However, we show by unit recordings the responses transmitted by the receptor neurons by means of extracellular electrodes, in the frog or in the mouse, that the same olfactory neuron can respond to molecules as different as camphor, acetophenone and cyclohexanone. This either demonstrates a "broad" receptor specificity, or negates the hypothesis of an expression of a unique odor receptor types by a given receptor neuron. The interaction of odorant ligands and membrane receptors is followed by a cascade of enzymatic reactions that perform the transduction of the chemical signal into a nerve message. There would be at least two second intracellular messengers involved in olfactory transduction, and recruited by two groups of distinct odorants. We show that some olfactory receptor neurons of the frog respond to substances belonging to both groups suggesting therefore that both transduction mechanisms are present simultaneously in at least some receptor neurons… With A. Duchamp, we were interested in the transformation of peripheral information by bulbar integration. Thus we compared the sensitivity profiles of the olfactory receptor neurons and those of the deutoneurones of the olfactory system (mitral cells) of the frog. We noted that although mitral cells are on average more selective than olfactory receptor neurons, their sensitivity profiles remain close to those registered at the periphery. Furthermore, in mice we have examined the topographical, glomerular distribution of peripheral activations transmitted to the deutoneurones of the system via primary fibers. The anatomo-functional analysis of these epithelio-bulbar projections by means of the metabolic labeling by the 2-deoxyglucose method suggests a strong convergence of certain peripheral fibers towards bulbar foci, and, at the same time, the existence of a more extensive or diffuse glomerular response. A functional convergence is thus superimposed on the anatomical convergence. However, it is difficult to believe that all the specific information of the stimulus resides in these foci since the lesions, localized or even extensive of the olfactory bulbs, do not prohibit the manifestation of olfactory guided behaviors learned before injury. These data are then discussed. Specific anosmia is a partial, hereditary deficiency of olfactory perception that selectively concerns a few odorous substances only and which is found essentially in humans. One of the explanations for this deficiency is that it shows a deficiency in membrane receptors normally involved in the recognition of these odorous substances. By studying an animal model of anosmia specific to isovaleric acid proposed by our predecessors, we first discover that the trouble is rather a specific hyposmia. We show that not all individuals of the strain are affected identically. Using electrophysiological recordings of the olfactory mucosa or anatomo-functional study of bulbar projections, we show that the periphery of the olfactory system of these mice that are considered to be specifically anosmic to isovaleric acid is sensitive to this substance. However, our results also demonstrate a deficit of the specific alteration of the sensitivity of the olfactory mucosa to the stimulus in these affected mice and differences in topological projections to the olfactory bulb by comparison with a control strain. These both results are compatible with the hypothesis of peripheral receptor deficiency. However, the design of an odorant coding by multiple different receptor interactions (the combinatorial code) does not fit well with the existence of "specific anosmia". The type of selectivity of the olfactory receptor neurons towards the odorant molecules that we observe indicates that, generally, an odor molecule interacts with several receptors, and suggests that the peripheral representation characteristic of the odorant is a detailed description of the stimulus inscribed in a plurineuronal activation pattern. This description is opposed to the design of a coding by dedicated channels (labeled lines), according to which very selective channels, closely tuned to stimuli, would encode the odorant. Our data do not make it unthinkable, certain neurons of this type, escaping our observation because of their high selectivity, could coexist with the less selective neurons that we generally observe. Geneticians have now to explain us how broad specific receptors can be selected to stay in a genome... In other respect, Knowing better the peripheral mechanisms of the olfactory discrimination, one can hope to find keys to organize the space of the smells. In the last paragraphs of our thesis, we have examined to what extent this hope can be filled.
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Submitted on : Tuesday, October 2, 2018 - 2:35:21 PM
Last modification on : Thursday, November 7, 2019 - 10:46:01 AM
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Gilles Sicard. DISCRIMINATION NERVEUSE OLFACTIVE et REPRESENTATION DE L'ODEUR PAR LE SYSTEME OLFACTIF. Sciences du Vivant [q-bio]. Université Claude Bernard, Lyon 1, 1998. Français. ⟨tel-01885961⟩

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