The Regulation Of parabss1 By spen And brm And Its Role In Seizure Susceptibility And Nociception Sensitivity In Drosophila

Seizures are defined by abnormal and synchronous firing of neurons within the central nervous system and epilepsy is persistent, spontaneous seizures. Single gene mutations have been linked to several epileptic disorders with most mutations occurring in voltage-gated channel genes. Many of these voltage-gated channels have highly conserved homologs in Drosophila melanogaster making flies a highly relevant model for studying human seizure disorders. In flies, mutations in the paralytic (para) voltage-gated sodium channel gene can cause seizure susceptibility. Flies with the para[bss1] mutation experienced a significant increase in seizure sensitivity compared to wild-type flies. para[bss1] mutants carrying the brm mutation were found to retain almost no seizure susceptibility while mutants carrying the spen mutation retained their seizure susceptibility, but it was significantly reduced. Flies with the parabss1 mutation also expressed a decrease in sensitivity to thermal stimuli at 46°C. From our results we determined that increased neuronal excitability in para[bss1] mutants may have led to a decrease in synapse size to control for this increase in neuronal excitability. Upon a mechanical stimulus to produce seizures or a nociceptive stimulus, this decreased synapse size might have led to a weaker synaptic output