Abstract
Human neurological diseases such as epilepsy and Parkinson's disease are associated with visual deficits that can be measured both psychophysically and with electrophysiological methods. Until recently, however, it has been difficult to examine the physiological and genetic origin of these deficits directly. Drosophila melanogaster (the fruit fly) is a common animal model of neurological disease with a relatively simple visual system and excellent genetic tractability but relatively little is know about the effects of genetic disease on the visual responses in this organism.
Here, we show that electrophysiological recordings of steady-state visually-evoked responses in Drosophila are qualitatively similar to those from humans and that spectral analysis of the evoked waveform can distinguish between different stages of the visual pathway. We also demonstrate that contrast masking and non-linear interactions between frequency-tagged signals are similar in both species and that they can be described by similar equations.
These SSVEP measurements are highly informative as to the presence and nature of genetic neurological diseases. For example, flies carrying the hLRRK2-G2019S transgene associated with human Parkinsons Disease exhibit significant gain control abnormalities immediately after eclosion while flies models of epilepsy also have reduced gain control, weaker contrast adaptation and increased response noise at this stage.
Finally, we show that this technique can be used to assay drug treatments. Specifically, we show that two novel, candidate Parkinson's Disease drugs normalize the SSVEP phenotype in G2019S flies. The SSVEP therefore represents a bridge between human and invertebrate studies of neurological disease and provides an in vivo method for monitoring the effects of drug treatment at a very early screening stage.