PAROXYSMAL DISCHARGES IN THE EL MOUSE, A GENETIC MODEL OF EPILEPSY

The EL/Suz (EL) mouse is a strain that is highly susceptible to convul sive seizures after repeated sensory stimulation. Its control strain, DDY/Jc1 (DDY), is less susceptible under similar conditions. The seizu re prone phenotype is the result of differences at several genetic loc i. In vivo electrical recordings from the seizure prone EL mouse brain have shown that the appearance of abnormal discharges in the hippocam pus are critical to the onset of generalized seizures, indicating that the hippocampus plays an important role in EL mouse seizure activity. In the present study, electrophysiological differences between EL and DDY mice (9-15 weeks of age) were examined by comparing field potenti als recorded from the dentate granule cell layer of hippocampal brain slices from mice that had not been stimulated to induce seizures. In c ontrol physiological solution, no significant differences were observe d in characteristics of perforant path evoked field potentials or in p aired pulse depression of evoked field potentials using 20 to 300 ms i nterstimulus intervals. After 60 min of disinhibition following bicucu lline (10 mu M) exposure, however, prolonged large amplitude potential s, paroxysmal discharges, were evoked by perforant path stimulation in the dentate gyrus of EL mice but were absent in the DDY strain. Parox ysmal discharges were curtailed by APV and were similar to responses r ecorded from the dentate gyrus in hippocampal brain slices from tempor al lobe epileptic patients. The field response to hilar stimulation wa s identical in both strains and was composed of a single population sp ike before and after bicuculline exposure. Messy fiber terminals were not present in the molecular layer of either strain. We propose that t he mechanisms leading to a greater likelihood of paroxysmal discharge generation in EL mouse may be important in the development and/or gene ration of epileptic seizures in this mouse strain and may be a signifi cant phenotypic difference between the EL mouse and its parent strain. (C) 1997 Elsevier Science B.V.