Non-synaptic mechanisms exert a powerful influence on seizure threshold. Dr. Jefferys among others established that non-synaptic mechanisms are actually sufficient in themselves to induce seizures and illustrated by epileptiform activity induced in hippocampal slices by reducing extracellular Ca2+ concentration. We showed that non-synaptic epileptiform activity can also be readily induced in-vitro in normal (2 mM) Ca2+ levels. Though of-course in the brain synaptic and non-synaptic mechanisms of both present, given that non-synaptic mechanisms are sufficiently powerful to start, propagate, and terminate electrographic seizures in themselves, it would seem that any comprehensive approach to understanding and treating epilepsy should not ignore non-synaptic mechanisms.

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