Neurophysiology of Drosophila Models of Parkinson’s Disease

Figure 6

Rescue of dopaminergic LRRK2-G2019S visual neurophysiology by BMPPB-32 only applied during adult life. (a) Diagram of the fly eye, showing the lens (red), photoreceptors (blue), second-order lamina (purple), and third/fourth-order medulla (orange). Dopaminergic neurons are shown in green. When illuminated with flickering blue light, the overall (field) potential we record is separated by the fast Fourier transform (FFT) into components corresponding to the photoreceptor, lamina, and medulla neurons, respectively, details in [15]. (b) Larvae were raised on drug free food and some transferred to food containing 2.5 μM of the specific LRRK2 kinase inhibitor BMPPB-32 [15] on the first day of adult life. After 3 days, the contrast/response function (CRF) of flies expressing LRRK2-G2019S in the dopaminergic neurons (DA → G2019S) is indistinguishable from flies expressing hLRRK2 or to those not expressing any transgene. BMPPB-32 application has no effect. (c) At 7 days, the DA → G2019S flies show very much reduced CRFs, well below the controls. BMPPB-32 restores the visual function to within 30% of the controls. There is no statistically significant effect of this drug on the control genotypes. Genotypes as in [15]; data not previously published.