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

• α-synuclein expression in 15 fly brain dopaminergic neurons induces locomotor defects
• These neurons selectively innervate the mushroom body β and β′ horizontal lobes
• β and β′ lobe projections of these neurons degenerate in the presence of α-synuclein
• Blocking mushroom body β′, but not β, lobe activity inhibits startle-induced locomotion

SummaryExpression of the human Parkinson-disease-associated protein α-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 β and β′ lobes of the mushroom bodies, and their connections to the Kenyon cells are markedly reduced when they express α-synuclein. Using selective mushroom body drivers, we show that blocking or overstimulating neuronal activity in the β′ lobe, but not the β or γ lobes, significantly inhibits negative geotaxis behavior. This suggests that modulation of the mushroom body β′ lobes by this dopaminergic pathway is specifically required for an efficient control of startle-induced locomotion in flies.

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