AGE-DEPENDENCE OF NMDA RECEPTOR INVOLVEMENT IN EPILEPTIFORM ACTIVITY IN RAT HIPPOCAMPAL SLICES

The pattern of epileptiform activity recorded from a number of in vitr o seizure models is age dependent: ictal discharges are observed in im mature brain slices while interictal bursts are seen in adult brain sl ices. This study evaluated the involvement of the N-methyl-D-aspartate (NMDA) receptor in the age-dependency of epileptiform activity record ed in area CAI of hippocampal slices in Mg2+-free medium. Incubation i n Mg2+-free medium induced ictal activity in 84% of hippocampal slices from immature rats (postnatal 10-15 days). In contrast, adult slices responded with interictal bursting, while ictal activity was rare (9%) . Bath application of the NMDA receptor antagonist D,L-2-amino-5-phosp honovaleric acid (DL-APV, 20 mu M) converted ictal activity to interic tal activity in the hippocampal slices from immature rats. In adult sl ices, bath application of NMDA (10-20 mu M) in Mg2+-free medium induce d ictal-like discharges. Perfusion with NMDA (20 mu M) in a medium con taining 1.5 mM Mg2+ induced ictal activity in immature slices while it evoked only interictal bursts in adult slices. These results suggest that differences in NMDA receptor function may be involved in the age- dependency of epileptiform activity induced by Mg2+-free medium. Enhan ced NMDA receptor-mediated activity may partially underlie increased s eizure susceptibility in the immature brain.