Animal models in epilepsy research: legacies and new directions

In this Perspective article, Brian Grone and Scott Baraban examine some of the numerous nonhuman animal models of epilepsy. The authors outline how traditional animal models have advanced our understanding of seizure initiation and epileptogenesis and also describe how the use of more 'non-traditional' model systems may further improve insight into both disease mechanisms as well as potential therapeutic avenues. Human epilepsies encompass a wide variety of clinical, behavioral and electrical manifestations. Correspondingly, studies of this disease in nonhuman animals have brought forward an equally wide array of animal models; that is, species and acute or chronic seizure induction protocols. Epilepsy research has a long history of comparative anatomical and physiological studies on a range of mostly mammalian species. Nonetheless, a relatively limited number of rodent models have emerged as the primary choices for most investigations. In many cases, these animal models are selected on the basis of convenience or tradition, although technical or experimental rationale does, and should, factor into these decisions. More complex mammalian brains and genetic model organisms including zebrafish have been studied less, but offer substantial advantages that are becoming widely recognized.