Sequence of events leading to seizure activity at the level of a hippocampal epileptic pacemaker

Abstract

An analysis of the sequence of synaptic events leading to seizure activity was performed in chronic awake animals at the level of a hippocampal “epileptic pacemaker” by recording with extracellular microelectrodes the responses induced by ipsilateral and contralateral hippocampal stimulation, in different layers of the field CA1 of the dorsal hippocampus. The first event marking the beginning of the epileptic buildup was an increased voltage and a delayed decay of the apical positive slow wave. Superimposed on it, spike discharges were recorded; some of them were developed at the peak of the wave, and some others superimposed on the falling phase of the slow wave. Later during stimulation similar changes occurred at the level of the basal dendrites, where a slow negative wave was potentiated during the epileptic buildup. The active involvement of pyramidal soma occurred later still during the buildup apparently as a consequence of orthodromically conducted dendritic spikes. An initial positive field was abruptly replaced by a long-lasting negative field with discharges and later on with spike inactivation. Concurrently with the first preepileptic changes of apical dendritic potential, somatic unitary small-amplitude discharges (probably from interneurones) were recorded at the apical dendritic level. Their frequency and number gradually increased during the epileptic buildup. It is assumed that the epileptogenic buildup developed independently at the apical and basal dendritic levels. An estimation of current density lines showed separate sinks and sources of current at the two levels during the preseizure period. The main excitatory changes occurred at the apical dendritic level, in spite of the positivity of the preepileptic wave at this level. It is probable that reverberating neuronal chains were built up between usually inactive interneurons and the apical dendritic branches. Pyramidal discharges probably reactivated the interneurons.