Modifications of seizure susceptibility in Drosophila. Daniel Kuebler2 and Mark A. Tanouye1,2. 1Department of Environmental Science, Policy and Management, Division of Insect Biology, University of California, Berkeley, California 94720 and 2Department of Molecular and Cell Biology, Division of Neurobiology, University of California, Berkeley, California 94720.
APStracts 6:0527N, 1999.
In a given population, certain individuals are much more likely to have seizures than others. This increase in seizure susceptibility can lead to spontaneous seizures, such as seen in idiopathic epilepsy, or to symptomatic seizures which occur following insults to the nervous system. Despite the frequency of these seizure disorders in the human population, the genetic and physiological basis for these defects remains unclear. The present study makes use of Drosophila as a potentially powerful model for understanding seizure susceptibility in humans. In addition to the genetic and molecular advantages of using Drosophila, we have found that seizures in Drosophila share much in common with seizures seen in humans. However, the most powerful aspect of this model lies in our ability to accurately measure seizure susceptibility across genotypes and over time. Here, we quantified seizure susceptibility in a variety of mutant and wild type strains and found that genetic mutations can modulate susceptibility over an extremely wide range. This genetic modulation of seizure susceptibility apparently occurs without affecting the threshold of individual neurons. Seizure susceptibility also varied depending on the experience of the fly, decreasing immediately after a seizure and then gradually increasing over time. We have also identified a novel phenomenon in which seizures are suppressed following certain high intensity stimuli. These results demonstrate the utility of Drosophila as a model system for studying human seizure disorders and provide insights into the possible mechanisms by which seizure susceptibility is modified.
Received 10 June 1999; accepted in final form 18 October 1999.
APS Manuscript Number J476-9.
Article publication pending Journal of Neurophysiology.
ISSN 1080-4757 Copyright 1999 The American Physiological Society.
Published in APStracts on 21 December 1999