Analysis of a Large Family of Candidate Taste Receptors

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.

Grant Number: 5R01DC011697-22
NIH Institute/Center: NIH
Principal Investigator: John Carlson