Identifying Neural Substrates of Behavior in Drosophila

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The goal of this research program is to exploit, and further develop, techniques for manipulating neural activity to identify the brain circuits underlying specific behaviors. Using the Gal4-UAS gene targeting system of Drosophila melanogaster to drive the expression of genes whose products enhance or inhibit neuronal excitability, we are selectively up- or down-regulating the activity of subsets of neurons and analyzing the effects of these manipulations on behavior. We are particularly interested in the suite of hormonally coordinated and developmentally programmed behaviors executed by the adult fly shortly after emergence from the pupal case, with a focus on those necessary for wing expansion. To identify neuronal substrates of these behaviors we use two approaches: one in which defined subsets of neurons, and the other in which random subsets, are inhibited (using Gal4 lines with defined promoters and Gal4 enhancer-trap lines, respectively). In each case, patterns of suppression or enhancement that affect the behaviors of interest are identified for further characterization. Using the first approach, we have found that inhibition of electrical activity in a small subset of neurons that express the neuromodulators serotonin, CCAP (crustacean cardioactive peptide) and bursicon suppresses wing expansion in flies. Using the second approach, we have identified 23 patterns of suppression (i.e. enhancer-trap lines) that generate wing expansion deficits. By further restricting these patterns using fly lines that inhibit Gal4 transcriptional activity in overlapping subsets of cells (using Gal80) we plan to identify and characterize the cells responsible for generating these deficits. Our investigation of the neuronal substrates underlying wing expansion behavior should serve as a ?proof of concept? of a circuit mapping approach that can later be extended to studies of mammalian behavior.