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Odors that Modify CO2 Receptor Activity in Insects and Their Effect on Innate CO2-Mediated Behavior and Neuronal Plasticity

Abstract

CO2 present in exhaled air is considered to be one of the most important olfactory cues for mosquitoes, causing activation of long-distance host-seeking flight behavior, as well as increased sensitivity to other skin odors. Here I show that volatile odorants from fruit can strongly inhibit the CO2 receptor in Drosophila melanogaster and completely abolish CO2-mediated behavior. Using the `empty neuron' in vivo expression system we establish that the odorants act directly on the CO2 receptor Gr21a/Gr63a. Following my work on italic>Drosophila , I have used electrophysiology assays to perform a comprehensive analysis of structurally related odorants in multiple vector mosquito species that have conserved CO2 receptor proteins. I have identified three novel classes of odorants that dramatically alter the response of the CO2-sensitive neuron. Detailed behavioral analyses for some of these odors show a dramatic disruption in the ability of mosquitoes to be attracted to CO2, offering a powerful approach to develop a new generation of insect repellents and lures that can reduce the ability of mosquitoes to seek out humans. While looking for inhibitors of the CO2 response, I have also studied italic>Drosophila Stress Odor as well as other activators of the CO2 neurons across italic>Drosophila species to investigate the role of these odors in the ecology of the fruit fly. In addition, I have investigated whether an odor-rich environment shapes the development of the olfactory system. Olfactory stimuli may regulate chemosensory gene expression and neuronal plasticity in invertebrates which could potentially alter the perception of odor stimuli and lead to significant behavioral modifications. I show that when flies are exposed to a CO2 inhibitory odor immediately after eclosion, a critical period in adult olfactory development, CO2 receptor expression is severely reduced. This reduced expression is reversed when the fly is removed from odor exposure indicating that neuronal cell death does not occur. In addition, I show that this odor exposure reduces expression of other antenna and palp specific odor receptors.

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