Chronic epileptic foci in vitro in hippocampal slices from rats with the tetanus toxin epileptic syndrome

Abstract

1. Minute doses of tetanus toxin were injected into the hippocampi of rats, under pentobarbitone anesthesia, to induce a chronic experimental epilepsy. The effects of this treatment were studied in vitro in hippocampal slices prepared 1-60 days after injection. 2. Epileptic activity was preserved in these slices in vitro, closely resembling that seen in vivo. Epileptiform afterdischarges were evoked by stimulation after survival times of greater than or equal to 3 days from injection. Spontaneous synchronous epileptic discharges were recorded from 7 days after injection. Both kinds of epileptiform activity were found with survival times up to 36 days but not beyond 44 days. This time course resembles the waxing and waning of the epileptic syndrome in vivo. 3. Two distinct types of spontaneous burst were seen. The first was a simple burst lasting 100-300 ms, reminiscent of the "interictal spike" of the clinical electroencephalogram. The second was much more prolonged, lasting several seconds. It consisted of a simple burst followed by a series of discrete afterbursts at 3-6/s and resembled the early stages of an epileptic seizure. Both types of burst were associated with slow field potentials that were positive at the cell-body layer. 4. Both the interictal and the seizure-like spontaneous epileptic discharges originated in the CA3b/c pyramidal cell region and propagated at 0.1-0.25 m/s along the cell layer toward the CA1 region. They occurred at very variable intervals, ranging from 20 s to 30 min. 5. Spontaneous epileptic bursts occurred in media containing 3 mM [K+]o to 5 mM in one-third of experiments during the period 1-4 wk after injection. Spontaneous bursts could be induced by increasing [K+]o to 5 mM in two-thirds of the remaining slices, which initially had produced evoked afterdischarges. 6. Intracellular recordings revealed that spontaneous field bursts were invariably associated with paroxysmal depolarization shifts (PDSs) and bursts of action potentials, suggesting that almost all the pyramidal cells in the region were recruited into the epileptic discharges. In some cells, smaller abnormal depolarizations were also seen; they were clearly larger than the spontaneous synaptic potentials but were not associated with field potentials. They may have been due to a more limited recruitment of pyramidal cells into partially synchronous bursts. 7. The tetanus toxin experimental epileptic syndrome differs from chronic models described previously in retaining in the hippocampal slice in vitro much of the spontaneous epileptic activity seen in vivo in the freely moving chronically epileptic rat.(ABSTRACT TRUNCATED AT 400 WORDS)