The purpose of this work is to elucidate the transformation of olfactory information in the first relay of the Drosophila brain, the antennal lobe. Elucidating how information propagates in a hierarchical system is an important step towards understanding sensory coding mechanisms. Olfactory coding is a useful model for revealing how sensory circuits generate, propagate and read a neural code to create sensory perception. The insect olfactory system is a tractable system for deciphering mechanisms of sensory processing because they achieve odor discrimination with simpler circuits than that of mammals. Furthermore, Drosophila offers a powerful set of molecular tools available to manipulate individual elements of the underlying circuit. In a preliminary set of experiments, we have found anatomical and physiological evidence for GABAB modulation of olfactory receptor neurons in Drosophila. We find the receptor provides a mechanism to extend the dynamic range of the system, and surprisingly we find that level of presynaptic inhibition is heterogeneous between input channels. We hypothesize that GABAB expression in select neurons provides a mechanism for behaviorally relevant feedback modulation of olfactory input. We propose a set of experiments to further investigate the mechanism of feedback inhibition on a molecular, physiological and behavioral level. We use molecular techniques to characterize the receptor expression, and two-photon imaging of calcium and synaptopHluorin to monitor presynaptic activity and synaptic transmission. We will test the hypothesis that feedback inhibition provides a mechanism for olfactory adaptation and dynamic range expansion. The results will provide new insight into modulation of sensory input in the olfactory system and the findings could provide new insight into the function of feedback inhibition in detection of behaviorally relevant cues. Relevance to public health. Elucidating mechanisms of sensory perception is pivotal to understanding how sensory systems function normally and in disease. We study modulation of the sensory input signal in the fly olfactory system because of its relative simplicity and the powerful set of molecular tools for cutting edge science that is more difficult in other animals. The work of this proposal is basic science that seeks to reveal basic principles about the sensory nervous system creating a knowledge base from which future medical and technical research can stem. Such work may reveal fundamental circuit properties applicable to larger more complex circuits and neural functions that are relevant to neurological disorders of sensory systems.
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