A Single Dopamine Pathway Underlies Progressive Locomotor Deficits in a Drosophila Model of Parkinson Disease

Expression of the human Parkinson-disease-associated protein alpha-synuclein in all Drosophila neurons induces progressive locomotor deficits. Here, we identify a group of 15 dopaminergic neurons per hemisphere in the anterior medial region of the brain whose disruption correlates with climbing impairments in this model. These neurons selectively innervate the horizontal beta and beta' lobes of the mushroom bodies, and their connections to the Kenyon cells are markedly reduced when they express alpha-synuclein. Using selective mushroom body drivers, we show that blocking or overstimulating neuronal activity in the beta' lobe, but not the beta or gamma lobes, significantly inhibits negative geotaxis behavior. This suggests that modulation of the mushroom body beta' lobes by this dopaminergic pathway is specifically required for an efficient control of startle-induced locomotion in flies.