Functional and Morphological Changes in the Hippocampal Neuronal Circuits Associated with Epileptic Seizures

Purpose: We review what is currently known about functional and morphologic plasticity of hippocampal neuronal circuits in animal epilepsy models. Results: Perforant‐path kindling has been shown to enhance excitatory synaptic transmission in the dentate gyrus significantly, and this enhancement has lasted for ≥1 month after kindling. However, in our rapid kindling experiment with an interstimulus interval of 5 min, perforant‐path kindling resulted in behavioral convulsions and prolonged the afterdischarge duration, but dentate synaptic transmission remained depressed during kindling. Conclusions: These results indicate that kindling‐induced synaptic potentiation is not necessary for kindling development. Conversely, epileptic seizures have led to the anomalous sprouting of mossy fibers, a process thought to induce hyperexcitation of granule cells. We conclude that the sprouting of mossy fibers did not play a critical role in kindling, because we observed no significant correlation between the mossy fiber sprouting and kindling development. Epileptic seizures also have been shown to increase γ‐aminobutyric acid (GABA)A receptor–mediated inhibition during interictal periods. Although this strengthening of GABAergic inhibition is likely to be a defensive measure against seizure initiation, some studies have suggested that another type of GABAergic response facilitates seizure activity. The possibility of GABAA receptor–mediated excitation during ictal periods is theoretically examined.