Dopamine Kinetics in a Drosophila Model of Parkinson Disease

Parkinson disease (PD) is a neurodegenerative movement disorder, with motor
symptoms caused by the death of dopaminergic cells in the central nervous
system. RING finger protein 11 (RNF11) has been identified in vulnerable
neurons of the substantia nigra in Parkinson disease patients, and localized to
the Lewy bodies of humans with idiopathic disease. In order to study the effects
of RNF11 on dopamine neurotransmission, it was necessary to improve the
techniques to detect dopamine at a millisecond time scale in Drosophila. Pulsed
light stimulations were used alongside Michaelis-Menten modeling to
characterize release and uptake of dopamine upon optogenetic stimulation. In
order to avoid the electrochemical defect at the switching potential caused by
blue light, a red light activated channelrhodopsin, CsChrimson, was
characterized and used to measure from a novel region of the central nervous
system, the protocerebrum. Using these new techniques, we tested the
hypothesis that RNF11 modulates dopamine neurotransmission in Drosophila
larvae. We identified RNF11 as a protein that may be a target for timely
intervention and pharmacological prevention of Parkinson disease progression.