Excitatory and inhibitory control of epileptiform discharges in combined hippocampal/entorhinal cortical slices

Abstract

We examined whether epileptiform activity can be induced and prevented by mild reduction of GABA A receptor-mediated inhibition and non-NMDA receptor-mediated excitation, respectively, in different regions of combined hippocampal/entorhinal cortical slices from juvenile rats (P15–21). We used the receptor antagonists bicuculline (GABA A) and CNQX (non-NMDA) as tools to investigate the sensitivities of the CA1, the subiculum (SUB) and the medial entorhinal cortex (MEC) for generating epileptiform discharges upon extracellular stimulation. We found that low concentrations of bicuculline (<3.5 μM) were enough to induce epileptiform discharges in the three regions. These discharges were similar to those observed under high concentrations of bicuculline (>10 μM) and consisted of stereotyped population bursts, recorded both extra- and intracellularly. Interestingly, the CA1 and SUB were more susceptible to generate discharges compared to the MEC in the same slices. We also found that non-NMDA excitation was critical in controlling discharges, as they were blocked by CNQX in a concentration-dependent manner. The sensitivity of the CA1 region to CNQX was lower than that of the SUB and MEC. Based on these regional differences, we show that epileptiform activity can be pharmacologically isolated within the CA1 region in the hippocampal–entorhinal circuitry in vitro.