OLFACTORY MIXTURE INTERACTIONS--MECHANISMS AND EFFECTS

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The broad objective of this proposal is to understand molecular, cellular, and systems level mechanisms responsible for the transduction, detection, and discrimination of odorant mixtures and their components. This includes gaining an understanding of (i) mechanisms of mixture interactions and olfactory transduction and (ii) the effects of mixture interactions on neural coding and behavioral discrimination of stimulus quality and intensity. We will use the spiny lobster (Panulirus argus) as the experimental animal system, and the stimuli will be a set of 7 odorant compounds -- AMP, betaine, cysteine, glutamate, succinate, taurine, and ammonium -- for which binary mixture interactions have already been defined from studies of behavior and of extracellular electrophysiology of olfactory receptor cells. The specific aims are the following: (I) Examine the role of competitive and noncompetitive inhibition of binding between odorant compounds for binding sites on olfactory receptor cell membrane in the generation of mixture interactions, using biochemical techniques. The location of these binding sites in the olfactory organ will also be determined, using transmission electron microscopy. (II) Determine the electrical basis of mixture interactions involving the above 7 compounds, using whole cell patch clamp techniques to study (a) the excitatory and inhibitory responses to single compound odorants and their binary mixtures and (b) the ionic dependence of these responses. This research is significant in that it and other work will generate, for the same species and the same set of chemicals, an understanding of olfactory events -- from receptor-odorant binding, to generation of ionic conductances, receptor potentials, and action potentials in receptor cells, to behavior -- that govern the transduction, detection, perception, and discrimination of odorant mixtures.