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The Journal of Neurophysiology Vol. 83 No. 2 February 2000, pp. 998-1009
Copyright ©2000 by the American Physiological Society
1Department of Molecular and Cell Biology, Division of Neurobiology; and 2Department of Environmental Science, Policy, and Management, Division of Insect Biology, University of California, Berkeley, California 94720
Kuebler, Daniel and
Mark A. Tanouye.
Modifications of Seizure Susceptibility in
Drosophila. J. Neurophysiol. 83: 998-1009, 2000. 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 that
occur after 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, it has been found that seizures in
Drosophila share much in common with seizures seen in
humans. However, the most powerful aspect of this model lies in the
ability to accurately measure seizure susceptibility across genotypes
and over time. In the current study seizure susceptibility was
quantified in a variety of mutant and wild-type strains, and it was
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. A novel phenomenon was also identified in which
seizures are suppressed after 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.
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