Age dependence of NMDA receptor involvement in epileptiform activity in rat hippocampal slices

Abstract 

The pattern of epileptiform activity recorded from a number of in vitro seizure models is age dependent: ictal discharges are observed in immature brain slices while interictal bursts are seen in adult brain slices. This study evaluated the involvement of the N-methyl-d-aspartate (NMDA) receptor in the age-dependency of epileptiform activity recorded in area CA1 of hippocampal slices in Mg²⁺-free medium. Incubation in 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-phosphonovaleric acid (DL-APV, 20 μM) converted ictal activity to interictal activity in the hippocampal slices from immature rats. In adult slices, bath application of NMDA (10–20 μM) in Mg²⁺-free medium induced ictal-like discharges. Perfusion with NMDA (20 μM) in a medium containing 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. Enhanced NMDA receptor-mediated activity may partially underlie increased seizure susceptibility in the immature brain.

Keywords:  Seizure susceptibility, N-methyl-d-aspartate (NMDA), Hippocampus, Development

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