Computer models of hippocampal circuit changes of the kindling model of epilepsy.

Abnormalities in the organization of brain circuits may underlie many types of epilepsy. This hypothesis can best be evaluated in the case of temporal lobe epilepsy, where evidence of rewiring (synaptic reorganization) can be found in the dentate gyrus. Computer modeling of normal and reorganized dentate gyrus was used to understand the functional consequences of these structural changes. Hyperexcitability appeared to be largely limited by the powerful intrinsic adaptation characteristic of granule cells, the principal cells in this area. Combining disinhibition with new recurrent excitatory circuitry was necessary to produce repeated firing of these cells. Paradoxically, continuing regenerative activity was only seen with a large reduction in the strength of the inciting stimulus. Validation of these findings will require further physiological correlation.