Epilepsy and the plastic mind.

Seizures are linked to many neuroplastic changes within hippocampal circuits, including alterations in neurogenesis and dendritic growth in the dentate gyrus. How do brief seizures cause the long-term plastic changes in the hippocampus that are associated with recurrent epilepsy? Recent experiments by Ma and colleagues provide insights. They demonstrate an epigenetic mechanism for long-lasting neuroplastic changes that is both activity-dependent and brain region-specific. Focusing on Gadd45b, a DNA excision repair gene, they show it is up-regulated after electroconvulsive seizures or glutamate dependent activation of NMDA receptors. Gadd45b demethylates DNA regulatory elements in promoters of genes encoding fibroblast growth factor 1 and brain-derived neurotrophic factor, increasing the expression of these genes within granule neurons of the dentate gyrus. These changes in growth factor expression promote neurogenesis in the subgranular zone and dendritic growth in the granule cell layer of the dentate gyrus. Further regional and temporal differences in the proliferation of astrocytes and microglia after seizures were demonstrated by two additional studies. Together this work highlights how activity-dependent epigenetic modifications to DNA can alter gene expression with remarkable regional and cell type specificity.