Epilepsy and Drug Discovery in Larval Zebrafish

Talk Summary: Zebrafish (Danio rerio) have emerged as a promising and valuable model organism. The increasing popularity of this small vertebrate is evident from the growing numbers of publications and new discoveries associated with the use of zebrafish for studying development, brain function, human disease, and drug screening.

Owing to the development of novel technologies, the range of zebrafish research possibilities is constantly expanding with new imaging, electrophysiological, and gene editing tools enhancing traditional techniques. Despite the widespread success of zebrafish in the neuroscience community, epilepsy research using this organism is more limited. To address this issue, the Baraban Lab began to adapt larval zebrafish for epilepsy related studies almost twenty years ago.

With the rapidly expanding molecular and neuroscience tool box, the lab is now using zebrafish models mimicking human pediatric epilepsies with genetic causes. These genetically modified zebrafish are amenable to rapid drug screening, sophisticated behavioral analysis, long-term electrophysiological monitoring or whole-brain calcium imaging, and hold great potential to advance our understanding and treatment of epilepsy.

In this lecture, Scott Baraban, PhD (University of California San Francisco) will highlight the past and present techniques which have made, and continue to make, zebrafish an attractive model organism in epilepsy research. He will focus on SCN1 mutant zebrafish mimicking a catastrophic form of pediatric epilepsy known as Dravet syndrome, and the lab’s aquarium-to-bedside success screening repurposed drug libraries to identify novel lead compounds for this disorder. Dr. Baraban will also discuss our on-going efforts to use CRISPR/Cas9 genome editing technologies to generate zebrafish mutants for all known human epilepsy genes on the CURE EGI list.