REVERSIBLE LOSS OF DENDRITIC SPINES AND ALTERED EXCITABILITY AFTER CHRONIC EPILEPSY IN HIPPOCAMPAL SLICE CULTURES

The morphological and functional consequences of epileptic activity were investigated by applying the convulsants bicuculline and/or picrotoxin to mature rat hippocampal slice cultures. After 3 days, some cells in all hippocampal subfields showed signs of degeneration, including swollen somata, vacuolation, and dendritic deformities, whereas others displayed only a massive reduction in the number of their dendritic spines. Intracellular recordings from CA3 pyramidal cells revealed a decrease in the amplitude of evoked excitatory synaptic potentials. Gamma-aminobutyric acid-releasing interneurons and inhibitory synaptic potentials were unaffected. Seven days after withdrawal of convulsants, remaining cells possessed a normal number of dendritic spines, thus demonstrating a considerable capacity for recovery. The pathological changes induced by convulsants are similar to those found in the hippocampi of human epileptics, suggesting that they are a consequence, rather than a cause, of epilepsy.