Seizures in a Bang-Sensitive Epilepsy Model Impact Associative Learning in Drosophila Larvae

Abstract

The seizures associated with epilepsy in humans may impact their learning and memory, however, the mechanism of how the seizures themselves lead to these deficits is not clear. Drosophila mutant flies that have seizure phenotypes have been used effectively as a model for human epilepsy. In this study, we tested whether stimuli that induce seizures in Drosophila parabss mutants, a mutation in the fly sodium channel gene, affect learning. We used an adult conditioned courtship model and both rewarding and aversive associative learning assays in Drosophila larvae. For the conditioned courtship model, males exposed to mated females show depressed mating when placed with virgin females, suggesting that they learned from their rejection. In the larval paradigm, larvae are trained by pairing an odor (octanol or amyl acetate) with a reward (fructose) or an aversive stimulus (electrical shock) and then tested for learning by looking for movement towards or away from the odor they were trained on in a choice assay. We found that our wildtype CS stock and parabss mutants did not respond to octanol as a neutral odor but as an aversive one. Therefore, octanol was used to train in a positive associate learning task and amyl acetate was used in aversive assays. Our parabss stock performed almost as well as wildtype in learning in all of these assays, although other labs had reported learning deficits in these mutants. In addition, seizure induced through vortex in the adult learning paradigm and cold in the larval assay disrupted learning. These results suggest that learning deficits may be directly due to seizures rather than some other effect of the mutant. Author SummaryIn humans, seizures like those seen in epilepsy are associated with deficits in learning and memory. However, the link between the seizures and these deficits are not well understood and there is conflicting studies about what the characteristics of the seizure and the types of learning or memory affected. Animal model systems have been effectively used to study human disease and for this study, we chose the fruit fly, Drosophila melanogaster. Drosophila mutant flies that have seizures have been used to study human epilepsy and have similar types of learning and memory found in higher animals. We asked whether seizure induced in a fly mutant would disrupt learning and memory. We used several types of learning tasks, and both fly adults and larva. While the mutant flies performed almost as well as normal flies in all of these learning tasks, when they had seizures right after they learned a task, the learning was disrupted. These results suggest that learning deficits in humans may be directly due to seizures rather than something else