Different phases of afterdischarge during rapid kindling procedure in mice

Abstract

The basic mechanisms of hippocampal networks in epileptogenesis are not entirely understood. To help achieve a better understanding of these mechanisms, we studied the extra-cellular electrically evoked responses in the hippocampi of mice during rapid kindling. Kindling protocol was achieved by stimulating the dorsal right hippocampus six times daily for four days using bipolar electrodes to produce sub-convulsive electrical discharges. Motor responses and analyzed electroencephalographic recordings showed progression from partial complex seizures to generalized seizures associated with different consecutive patterns within the afterdischarges. A spike-wave pattern appeared immediately after stimulation in combination with a poly-spike complex superimposed over the wave (AD1). AD1 was followed by a poly-spike complex (AD2), which was followed by a progressive modification of repetitive spikes (AD3). An ictal depression event was observed at the end of each AD3. Theta oscillations were observed at stage 1-2 of kindling, while beta/gamma oscillations appeared within AD2, associated with stage 4-5 from Racine's score. Benzodiazepine, a GABA (A) agonist (Diazepam) administered at non-sedative doses and only on days 3 and 4 of kindling, limited beta and gamma frequency bands and the progression of seizure severity, suggesting that the failure of GABA (A) agonism mediates the propagation or generalization of seizures. We conclude that different phases of afterdischarge occur during kindling and that high frequencies mediate generalization of seizures.