Mechanisms of compensation for loss of brain dopamine

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DESCRIPTION (provided by applicant): Dopamine (DA) is an important neurotransmitter/ neuromodulator throughout the animal kingdom. In humans, dysfunction of the DA system leads to motor, cognitive, and affective disorders. Detailed studies feasible in the genetic model system Drosophila melanogaster permit circuit level definition of pathways responsible for specific behaviors, allow for detailed temporal/spatial control of DA synthesis, and have the potential to uncover novel neural mechanisms relevant to human diseases of DA dysfunction. In this proposal, we study a novel and spontaneous suppression of a subset of dopamine-loss phenotypes. We will use genetic and molecular techniques to identify and characterize the genetic elements responsible for this suppression. Our model is particularly relevant to early stage Parkinson's disease, where a poorly described pathway can partially compensate for decreased DA levels, delaying appearance of symptoms. This proposal focuses on the mechanisms of this compensation.