Knockdown Modulates Dopamine Release in the Central Complex, but Not the Mushroom Body Heel, of Aging .

Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic neurons leading to reduced locomotion. Mutations of gene in produce the same phenotypes as vertebrate models, but the effect of knockdown on dopamine release is not known. Here, we report age-dependent, spatial variation of dopamine release in the brain of -RNAi adult . Dopamine was repetitively stimulated by local application of acetylcholine and quantified by fast-scan cyclic voltammetry in the central complex or mushroom body heel. In the central complex, the main area controlling locomotor function, dopamine release is maintained for repeated stimulations in aged control flies, but lower concentrations of dopamine are released in the central complex of aged -RNAi flies. In the mushroom body heel, the dopamine release decrease in older -RNAi flies is similar to controls. There is not significant dopaminergic neuronal loss even in older knockdown flies, which indicates that the changes in stimulated dopamine release are due to alterations of neuronal function. In young -RNAi flies, locomotion is inhibited by 30%, while in older -RNAi flies it is inhibited by 85%. Overall, stimulated dopamine release is modulated by in an age and brain region dependent manner. Correlating the functional state of the dopaminergic system with behavioral phenotypes provides unique insights into the PD mechanism. can be used to study dopamine functionality in PD, elucidate how genetics influence dopamine, and test potential therapies to maintain dopamine release.