Figure 1.

Induction of continuous seizure activity (status epilepticus) in cultured hippocampal neurons for 3 hr in the presence and absence of several neuropharmacological agents. Intracellular recordings were obtained from hippocampal pyramidal neurons before, during, and after a 3-hr low-Mg²⁺ treatment employing established procedures (7). The recordings shown were representative of more than 10 independent experiments for each condition. (A) A representative intracellular recording from a control neuron showing occasional spontaneous action potentials. The resting potential of individual neurons ranged from −65 to −50 mV. Recording from more than 100 control neurons, no spontaneous seizure activity was observed. (B–J) Representative intracellular recordings during low-Mg²⁺ treatment in normal (2 mM) (B) or low (0.2 mM) Ca²⁺ (C), or various neuropharmacological agents (see Fig. 2 D–J). During the low-Mg²⁺ treatment the cells developed longer-duration synaptic potentials and multiple action potentials, evolving into continuous tonic high-frequency (4–20 Hz) burst discharges. The frequency of burst discharges varied from cell to cell. However, all the conditions shown in C–J manifested 3 hr of continuous seizure discharge. The low Ca²⁺ 0.2 mM (C), APV 25 μM (E), and MK801 10 μM (F) treatments consistently produced higher-frequency discharges. NBQX 10 μM (H) and 5 μM nifedipine (I) produced slightly lower-frequency discharges. After readdition of normal Mg²⁺ levels to the medium, all spontaneous continuous discharges attenuated. SE produced less than 10% neuronal cell death under these conditions (7).