Role of hippocampus in epileptogenesis: new insights in the cross-talks between the underlying mechanisms

As a component of the limbic system, the hippocampal region, one of the deep structures of the medial temporal lobe, is a complex structure involved in a wide range of cognitive processes, including declarative memory, spatial memory, and emotional reactions. The subiculum, the dentate gyrus (DG), and the cornu of Ammonis (CA)-which includes the four subfields CA4, CA3, CA2, and CA1-make up the hippocampus. The hippocampus is known to have the lowest seizure threshold. Therefore, the hippocampus is relatively more prone to seizures, and plays a significant role in epilepsy. Also, it has been reported that seizures can result in abnormal hippocampal neurogenesis and malfunctioning circuits that impair hippocampal function. Several mechanisms have been suggested for the process of epileptogenesis including gliosis, neuronal degeneration, neurotransmitter disturbances, channelopathy, neuroinflammations, and axonal plasticity. In this review, we will focus on the role of the hippocampus in the process of epileptogenesis, as well as on the morphological changes in hippocampal structure, neuronal circuits, neurotransmitters and neurosteroids in epilepsy.