Methods and compositions for treating a seizure disorder are provided which include administering to the patient a vector encoding a modified receptor for delivery of the modified receptor to the target location, the modified receptor being modified to be activated by a synthetic ligand, wherein the modified receptor inhibits neuronal firing when activated; and administering to the patient the synthetic ligand. Also provided are methods and compositions for treating a seizure disorder in a patient in need thereof by administering to the patient a vector encoding a modified receptor for delivery of the modified receptor to the target location, the modified receptor being modified to be activated by a synthetic ligand, wherein the modified receptor increases neuronal firing when activated; and administering to the patient the synthetic ligand. The methods are used to improve or alleviate one or more symptoms of a seizure disorder.