The immune system occasionally launches a strike on one of its own proteins, generating self(auto)antibodies. Autoantibodies against brain proteins have recently been discovered in patients with difficult-to-treat epilepsies of unknown cause, including some that bind a secreted protein involved in communication called LGI1. This project will test models of autoantibody transfer to determine if these LGI1 antibodies are sufficient to cause seizures and interfere with brain functions such as memory. We will also look at the molecular changes that occur after exposure to the autoantibodies to understand the mechanism by which they promote seizures.