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 o f temporal lobe epilepsy, where evidence of rewiring (synaptic reorgan ization) can be found in the dentate gyrus. Computer modeling of norma l and reorganized dentate gyrus was used to understand the functional consequences of these structural changes. Hyperexcitability appeared t o be largely limited by the powerful intrinsic adaptation characterist ic of granule cells, the principal cells in this area. Combining disin hibition with new recurrent excitatory circuitry was necessary to prod uce repeated firing of these cells. Paradoxically, continuing regenera tive activity was only seen with a large reduction in the strength of the inciting stimulus. Validation of these findings will require furth er physiological correlation. (C) 1998 Elsevier Science B.V. All right s reserved.