Drosophila neurobiology is a powerful tool that could be used to uncover fundamental mechanisms underlying human neuropathic diseases. Drosophila mutants may be used to model idiopathic neurological disorders, and mutant phenotypes used to dissect apart the complex pathology that is often associated with human disorders. Here, we present a model for human periventricular heterotopia (PH): mutations of the Drosophila jitterbug (jbug) gene that cause bang-sensitive paralysis. Cortical malformations (dysplasia) are often associated with seizure and chronic epileptic disorders. PH is an inherited human disease that causes dysplasia, and is associated with epilepsy. Recently, the mutation responsible for this disease has been linked to the human filamin-1 (ABP-280) gene. jbug is a Drosophila filamin-like gene on the second chromosome (58F to 59A). A P-element insertion into this gene results in a mutant that is about 2 to 3 times more susceptible to seizure than wild type. Unlike the human mutation, we could not find any structural or axon guidance defects in the embryonic, larval or adult nervous system of the P-element allele. We are currently examining other alleles of jbug for structural defects. The current hypothesis regarding the relationship between cortical dysplasia and epilepsy centers on the abnormal neuronal networks that form due to abnormal development. The possibility that intrinsic properties of mutant neurons may contribute to seizure genesis has been largely ignored. jbug allows the study of possible seizure-genic property of neurons in a filamin mutant without the influence of gross anatomical defects. We have examined the properties of jbug nervous system using the adult giant -fiber (GF) and the larval neuromuscular junction (LNMJ) as our assays. We have found that at the LNMJ miniature EPSP frequency was increased in the mutant (2.7± 0.5Hz) when compared to wild type (1Hz). We have not found any defects associated with the adult giant -fiber system. Recently, we have discovered that jbug is also a cold-sensitive paralytic mutation. At 10ƒ C jbug flies paralyze within a minute; wild type flies are not affected for at least 5 minutes at this temperature. Interestingly, jbug is also more susceptible to seizure in cold temperatures. Currently, we are examining effects of temperature on the adult GF and LNMJ.
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