Seizure Activity Induced by Electroshock in <em>Drosophila</em> Larvae

Epilepsy presents a significant health burden that is exacerbated by high numbers of individuals who are drug-refractory. Whilst some drug-refractory patients do respond to non-drug treatments (e.g., vagal nerve stimulation, ketogenic diet, etc.), the last resort for many is challenging and expensive surgery to provide relief from seizures. Whilst it is generally acknowledged that antiseizure medications with a broader range of targets are required, the hurdle in achieving this is the identification of novel drug targets. Genetically tractable model animals offer promise in this regard. The fruit fly, Drosophila melanogaster, has become a powerful model for investigating the mechanistic basis of, and better treatments for, seizures. Many identified fly mutations result in larvae and adults exhibiting seizure-like activity in response to strong stimulation (electrical, mechanical, and/or thermal). Many of these mutations are in genes homologous to those that contribute to human genetic epilepsies (e.g., the voltage-gated Na⁺ channel). It is also now possible to replace a fly gene with its human equivalent that additionally, carries a disease-related mutation. Thus, the humble fly has become an avatar to model human disease. This study describes a suitable method to use Drosophila larvae for low to medium-throughput drug screens to identify unique compounds, and their targets, that have antiseizure potential.