PLASTICITY
Most cases of temporal lobe epilepsy are believed to develop after a brain lesion. Reactive growth triggered by seizure-induced injuries strengthens monosynaptic recurrent excitatory circuitry in several brain regions, including the dentate gyrus. Studies of the dentate gyrus in animal models demonstrated the formation of a novel granule-cell network in epileptic brain: granule cells, either having or not having a basal dendrite, and newly-generated hilar ectopic granule cells are synaptically interconnected by recurrent mossy fibers. Formation of this recurrent excitatory circuit is associated with a reduced threshold for granule-cell synchronization, and properties of hilar ectopic granule cells suggest this population could serve as the trigger for this synchronized discharge. However, homeostatic changes in the residual GABA innervation reduce excitability. Important, still to be elucidated, issues include: the circumstances under which reverberating excitation overcomes homeostatic restraints to synchronize population bursts, the mechanisms by which dentate gyrus inhibition recovers from the seizure-induced loss of GABA interneurons, the precise role of hilar ectopic granule cells in seizure propagation, and the extent to which reorganization of brain circuitry accounts for cognitive/behavioral dysfunction in persons with lesional epilepsy.
