Epilepsy-associated alterations in hippocampal excitability.

The hippocampus exhibits a wide range of epilepsy-related abnormalities and is situated in the mesial temporal lobe, where limbic seizures begin. These abnormalities could affect membrane excitability and lead to overstimulation of neurons. Multiple overlapping processes refer to neural homeostatic responses develop in neurons that work together to restore neuronal firing rates to control levels. Nevertheless, homeostatic mechanisms are unable to restore normal neuronal excitability, and the epileptic hippocampus becomes hyperexcitable or hypoexcitable. Studies show that there is hyperexcitability even before starting recurrent spontaneous seizures, suggesting although hippocampal hyperexcitability may contribute to epileptogenesis, it alone is insufficient to produce epileptic seizures. This supports the concept that the hippocampus is not the only substrate for limbic seizure onset, and a broader hyperexcitable limbic structure may contribute to temporal lobe epilepsy (TLE) seizures. Nevertheless, seizures also occur in conditions where the hippocampus shows a hypoexcitable phenotype. Since TLE seizures most often originate in the hippocampus, it could therefore be assumed that both hippocampal hypoexcitability and hyperexcitability are undesirable states that make the epileptic hippocampal network less stable and may, under certain conditions, trigger seizures.