Previous research has shown that visual sensitivity in human epilepsy patients is abnormal – characterized by increased responses at high contrast levels. These abnormalities have been linked to changes in neuronal gain control. Using animal models to study these changes is a useful approach. In this thesis, we used a steady-state visually evoked potential (SSVEP) technique similar to that used in humans to study photoreceptor-level and neuronal gain control in wild type (w-) Drosophila across a range of ages. We then compared these responses to those obtained from Drosophila carrying the kcc potassium channel mutation that renders young flies susceptible to light and shock-induced seizures. By taking into account the age and temperature dependence of the mutant (kccDHS1) flies, we were able to identify increased neural activity that recovers to the normal profile as they get older. We also found that these kccDHS1 flies are hypersensitive to light, particularly when young. These two findings are consistent with the fact that the level of the KCC protein increases with age. In addition, we found that kccDHS1 flies generate high frequency oscillations in their ERGs in response (50 – 100 Hz) to abrupt light onsets and offsets – a phenomenon that might be linked to abnormal changes in the gain control of neuronal feedback circuits.
Studying visual abnormalities in Drosophila can reveal important information but eventually we need to link any visual abnormalities observed in animal models to humans. We therefore, attempted to measure subtle changes in gain control in humans due to adaptation, and at the same time make use of the human mental ability to measure another measure of gain control, attention, using an fMRI technique. Although our data did not show any interaction between adaptation and attention, it suggests that attention in early visual pathways largely affects the level of suppression in non-stimulated regions around the adaptor rather than responses to the probe itself. This is a manipulation that links to our work on adaptation in Drosophila in Chapter 6.
Overall, the results presented in this thesis showed that fly models of epilepsy can be useful for studying changes in visual gain control, and showed that this work might be extended to humans
