Zinc and Epileptogenesis

Zinc is concentrated in the hippocampus, particularly in the mossy fiber axons of the dentate gyrus, and has been hypothesized to be important in neurodegeneration and epilepsy. Previous studies have suggested that activity-dependent release of zinc from reorganized mossy fibers leads to collapse of granule-cell inhibition. Synaptically released zinc has been proposed to depress the function of the new "epileptic" GABA(A) receptors, which have subunits that are zinc-sensitive. Recent experiments by Molnar and Nadler have replicated the previous data, and further tested this hypothesis. Their work suggests that activated mossy fibers in hippocampal slices do not release adequate zinc to depress GABA(A) receptor function at nearby inhibitory synapses. These studies point to the complexity of this hypothesis, particularly in regard to zinc release in vitro versus in vivo and the diffusion of zinc in the extracellular space.