DUSP4 appears to be a highly localized endogenous inhibitor of epileptic signaling in human neocortex

Epilepsy is a chronic debilitating disease. Once it develops, epileptic circuits often persist throughout life. Fortunately, in focal forms of epilepsy, these circuits can remain highly localized and are amenable to surgical resections, suggesting that endogenous mechanisms restrict their spread to other brain regions. Using a high-throughput genomic analysis of human epileptic brain regions, we identified DUSP4 as an activity-dependent inhibitor of MAPK signaling expressed in focal patches surrounding human neocortical epileptic brain regions. Our results suggest that DUSP4, through local inhibition of MAPK signaling, acts as an endogenous, spatially segregated safety mechanism to prevent the spread of epileptic activity. Augmenting DUSP4 expression could be a novel disease-modifying approach to prevent or treat human epilepsy.