Transition from normal to epileptiform activity in kindled rat hippocampal slices

We previously demonstrated kindling of synchronized bursts (ISs) by repeated sine-wave stimulation (SW: 2-5 sec, 60 Hz, 20-50 microA, every 5 min) in the CA2/3 area of rat hippocampal slices. Here we report the behavior of individual CA2/3 neurons during the kindling procedure. Intra- and extracellular recordings were obtained concurrently before, during and following SW. Test pulses and SWs were applied in CA2/3 or CA1 stratum radiatum. Neuronal response to to intracellular stimulation was tested by 100 msec depolarizing dc pulses or by 2-20 sec sinusoidal currents. The role of the N-methyl-D-aspartate (NMDA) receptor in the transition from normal responses to ISs was assessed by perfusing the slices with a specific antogonist (DL-2-amino-5-phosphono-valeric acid, APV, 50-200 microM). Our results show that kindling of ISs occurred in two steps: (1) via NMDA-dependent depolarizations during SW, or during SW-induced afterdischarges, and (2) through the recruitment of secondary, late EPSPs (1EPSPs), between consecutive SWs. ISs developed from the 1EPSPs, while the early responses (action potentials, EPSPs, and population spikes) remained unchanged. Kindling of ISs occurred with no changes in resting membrane potential, membrane resistance, or threshold of action potentials. APV did not block kindled ISs, but considerably reduced their amplitude and duration, and increased their frequency. These latter findings suggest that APV-insensitive mechanisms, activated through NMDA-dependent processes, were responsible for the triggering of ISs, and that NMDA receptor systems participated in the control of their rate of occurrence.