Analysis of a Large Family of Candidate Taste Receptors

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PROJECT SUMMARY The long-term goal of this project is to elucidate the mechanisms by which bitter tastants are detected and encoded. The experimental plan takes advantage of the fruit fly Drosophila as a model system, which allows molecular genetic analysis of taste genes and incisive electrophysiological analysis of taste function. The proposal takes advantage of a major advance in electrophysiology. Previous electrophysiological analysis of insect taste via "tip recording" was limited to the period during which taste neurons are in contact with a tastant. Technical innovation has now made it convenient to record the activity of taste neurons before, during, and after stimulation. It is now possible to analyze features of taste coding that have not been examined before. The first aim will determine the spontaneous firing frequency of taste neurons, and the molecular determinants of the frequency. It will examine whether inhibition of bitter taste neurons by bitter tastants occurs widely and represents a new degree of freedom for taste coding. The second aim proposes a precise and quantitative physiological analysis of OFF responses, which could not be observed with conventional electrophysiological analysis. The prevalence of these responses will be determined systematically. The study will test the hypothesis that the magnitude and dynamics of OFF responses carry information about the identity and intensity of taste stimuli. This aim should also provide information about the cellular and molecular mechanisms underlying OFF responses. Together this analysis should provide insight into a long-overlooked feature of taste coding. The third aim will define another remarkably understudied feature of taste coding: the inhibition of bitter neurons by sugars. It will quantify the inhibition of both spontaneous activity and OFF responses. The analysis will determine whether the inhibition depends on the quality and quantity of the sugar stimulus. The aim is also designed to provide insight into the mechanism of inhibition. Diseases carried by insects afflict hundreds of millions of people each year. These insects detect their human hosts largely through their chemosensory systems. Advances in understanding these chemosensory systems may lead to new means of manipulating them and of thereby controlling these insect vectors of human disease.