Lovastatin suppresses hyperexcitability and seizure in Angelman syndrome model

Epilepsy is prevalent and often medically intractable in Angelman syndrome (AS). AS mouse model (Ube3a(m - /P +)) shows reduced excitatory neurotransmission but lower seizure threshold. The neural mechanism linking the synaptic dysfunction to the seizure remains elusive. We show that the local circuits of Ube3a(m - /P +) in vitro are hyperexcitable and display a unique epileptiform activity, a phenomenon that is reminiscent of the finding in fragile X syndrome (FXS) mouse model. Similar to the FXS model, lovastatin suppressed the epileptiform activity and audiogenic seizures in Ube3a(m - /P +). The in vitro model of Ube3a(m - /P +) is valuable for dissection of neural mechanism and epilepsy drug screening in vivo.