The objective of this proposal is to carry out a comprehensive research program focused on the study of basic mechanisms of limbic epilepsy. The proposal brings together investigators with expertise in anatomy, biochemistry, pharmacology, physiology, and clinical epilepsy. These skills will be focused on studies of both the kindling and kainic acid models of epilepsy in the rat. The proposal also includes characterization of some physiologic processes in hippocampal formation, namely dendritic inhibition and spike frequency adaptation, and will assess whether alterations of these fundamental processes are involved in epilepsy. Biochemical and morphologic studies will be performed on hippocampal formation surgically removed from humans with medically intractable complex partial epilepsy. The ultimate goal of all components of this proposal is to further our understanding of the basic mechanisms of epilepsy from study of model systems. This information should provide a rational basis for new pharmacologic approaches designed to more effectively treat or prevent human epilepsy.