Chronic epilepsy in developing hippocampal neurons: electrophysiologic and morphologic features

Despite the susceptibility of immature neurons to seizures, there are few models of epilepsy in the developing brain. By taking advantage of activity-dependent developmental changes in young neurons, we have developed a novel model of chronic epilepsy in cultured hippocampal slices. Incubating slices in tetrodotoxin (TTX) for at least 1 week produced significant changes in the electrical activity and appearance of CA1 pyramidal neurons. Extracellular recordings revealed multiple population spikes, and, in whole-cell recordings, evoked synaptic potentials lasting hundreds of milliseconds with many superimposed action potentials were present. Spontaneous firing with burst-like discharges was also evident. These changes were secondary to increased AMPA-receptor-mediated responses and decreased GABA(A) receptor events. Altered membrane properties involved increased expression of T-type Ca(2+) channels which are normally down-regulated in these neurons. TTX-treated neurons also showed abnormal dendritic branching. This model of chronic epilepsy in developing hippocampal neurons demonstrated many changes at the membrane, cellular and synaptic level that may provide new insights into the nature of epileptogenesis in the young brain.