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 powerful Gal4-UAS gene targeting system of Drosophila melanogaster to drive the expression of genes whose products inhibit neuronal excitability or synaptic transmission, we are selectively inhibiting the activity of subsets of neurons and analyzing the effects of this manipulation on two behaviors: rest, the fly analog of mammalian sleep, and wing expansion, a hormonally coordinated and developmentally programmed behavior executed by the adult fly shortly after emergence from the pupal case. 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 that affect the behaviors of interest are identified for further characterization. Using the first approach, we have found that inhibition of electrical activity in cells that synthesize the neurotransmitters dopamine and serotonin suppresses both wing expansion and the locomoter activity underlying rest/activity cycles in flies. Our results implicate a role for serotonin-secreting cells in the former behavior. We are currently applying a variant of the MARCM technique to further restrict the pattern of suppression to determine which serotonergic cells are essential to generate the behavior. Using the second approach, we have identified 10 patterns of suppression (i.e. enhancer-trap lines) that generate wing expansion deficits. By further restricting these patterns we plan to identify and characterize the individual 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. The newly initiated work on rest is also expected to illuminate the mammalian neurocircuitry governing sleep given the similar molecular mechanisms underlying this evolutionarily conserved behavior.