Abstracts

Rationale: Dravet Syndrome, or Severe Myoclonic Epilepsy of Infancy (SMEI), is a severe and rare form of intractable childhood epilepsy, caused mainly by a mutation in the SCN1A gene that impairs the hippocampal inhibitory neuron excitability while the striatum excitatory neuron function is maintained causing an imbalance resulting in the epileptic activity Methods: By use of Axion Biosystems’s Maestro MEA (Multi Electrodes Array) systems, we captured, in vitro, the neuronal activity of both Wild Type (WT) and Knockout (KO) mice Hippocampus Inhibitory Neurons in the form of Spikes (NS), Bursts and Network Bursts (NB). Results: Compared to WT mice, KO mice had a maturement delay and took longer to start emitting NS and NB. Also, WT Hippocampus Neurons’ NB would start earlier but less than a month later would mostly be absent while in the KO Neurons it had a delayed start but grew exponentially. We theorized this is possibly due to NB blockage caused by unimpaired GABA activity in the WT mice as Hippocampus are known to have a significant percentage (10-20%) GABA neurons. When adding Biccuculine, a known GABA-Blocker to the WT cells we were able to notice a decrease in the number of NB, but they lasted for a longer compared to the non-Biccuculine cultures. Conclusions: These findings provide compelling evidence that the inhibitory neurons are affected by SCN1A mutations and that this system might be applicable for drug development as it opens up a new potential path for the treatment of Dravet Syndrome. Funding: AMED Grant