One of the major concepts that dominated the epilepsy research community in 1980s was the importance of underlying neuropathology in the hippocampus. For the purposes of this review, the hippocampus is defined as areas CA1, CA2, CA3, and the dentate gyrus (DG). There was a common view that temporal lobe epilepsy (TLE) was characterized by a pattern of hippocampal neuronal loss that was originally called Ammon’s horn or hippocampal sclerosis and then, as neuronal loss in extrahippocampal areas became appreciated, mesial temporal sclerosis (MTS).1 In the hippocampus, neuronal loss mainly included the DG hilus and pyramidal cell layers of areas CA1 and CA3. The DG and area CA2 cell layers were relatively resistant.1