Greater contribution of N-methyl- d-aspartic acid receptors in ventral compared to dorsal hippocampal slices in the expression and long-term maintenance of epileptiform activity

Abstract

Functional segregation along the dorso-ventral axis of the hippocampus is a developing concept. The higher susceptibility of the ventral hippocampus to epileptic activity compared with dorsal hippocampus is one of the main features, which still has obscure mechanisms. Using the model of magnesium-free medium and field recordings, single epileptiform discharges displayed higher incidence (77% vs 57%), rate (41.7±3.1 vs 13.5±0.7 events/min), duration (173.9±17.7 vs 116.8±13.6ms) and intensity (coastline, 25.4±2.5 vs 9.5±1.8) in ventral compared with dorsal rat hippocampal slices. In addition, the decay phase of the evoked synaptic potentials was 110% slower in ventral slices. The N-methyl- d-aspartate (NMDA) receptor antagonist d-(−)-2-amino-5-phosphonopentanoic acid (50–100μM) decreased the discharge rate and coastline similarly in ventral and dorsal slices, but it shortened the discharges in ventral slices (by 40%) only. The NMDA receptor antagonist 3-(( R)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (10μM) decreased the rate in both groups and additionally shortened discharges in both kinds of slices, an effect which was greater in ventral ones (31% vs 13%). Furthermore, both drugs shortened the evoked potentials more in ventral (77%) than in dorsal slices (52%). On the other hand, 1μM of 3-(( R)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid shortened the discharges and evoked synaptic potentials only in ventral slices, and slowed down the discharge rate only in dorsal slices. Addition of NMDA, in the magnesium-free medium, enhanced activity in both kinds of slices. At 5 and 10μM of NMDA 51% of the ventral but only 9% of the dorsal slices displayed persistent epileptiform discharges, which were recorded for at least one hour after reintroduction of magnesium in the medium. At 10–20μM the enhancement of activity was transient, followed by suppression of discharges in 40% and 76% of the ventral and dorsal slices, respectively. Most of the slices having experienced suppression did not develop persistent activity. We propose that the NMDA receptors contribute to the higher susceptibility of the ventral hippocampus to expression and long-term maintenance of epileptiform discharges. This diversification may be related to other aspects of hippocampal dorso-ventral functional segregation.