Despite the introduction of ~15 new anti-epileptic drugs (AEDs) over the past two decades, about one third of epilepsy patients will not be seizure free. It is these patients who carry the greatest burden of the disease. MiRNAs represent an entirely new potential target for the treatment and prevention of epilepsy and drug-like molecules targeting miRNAs (antagomirs) are now in clinical trials for other diseases. This workpackage will assess the impact of manipulating novel miRNAs on epilepsy in experimental models. This will utilize genetic approaches, including viral approaches through InteRNA (Netherlands) and antagomir or mimic-based delivery. Teams will assess the impact on gene expression in the brain, on seizures, pathology and behavior, and testing early vs late treatment.