Chapter 24 – Drosophila

The fruit fly, Drosophila melanogaster, is a genetic model system that has been exploited for epilepsy research for more than 30 years. Although clearly distant from mammals, the high degree of conservation that exists at both a molecular and physiological level provides the fly with many experimental advantages. Prominent among these advantages are the ability to rapidly discover new biology contributing to seizure and an ability to undertake high-throughput genetic and chemical screens. The recent development of gene-editing greatly increases the utility of this insect through the generation of humanized “knock-in” mutations. We describe the use of Drosophila for epilepsy research and highlight the methodology used to induce seizure activity. We also describe two case studies to convey how this model can best be used to increase understanding of seizure and to identify novel targets for next-generation drug design.