Abstracts

RATIONALE: Local excitatory circuits are thought to synchronize neuronal activity during seizures. Formation of new local excitatory circuits has been proposed to be one major contributor to epileptogenesis. This hypothesis was tested in the hippocampal CA1 area of the kainate-treated rat model of temporal lobe epilepsy.
METHODS: Whole-cell recordings of CA1 pyramidal neurons, with flash photolysis of caged glutamate as a focal excitant, were used to study local excitatory connections in CA1. Kainate-treated rats (N=15, 3-9 months after treatment), which had been observed to have spontaneous motor seizures, and saline-treated or age-matched control rats (N=6) were studied. All experiments were done in isolated CA1 minislices, and in the presence of bicuculline (30 [mu]M) to block GABAA-receptor-mediated inhibition.
RESULTS: Spontaneous excitatory postsynaptic currents (sEPSCs) were observed in 69% (27/39) of neurons from kainate-treated rats and in 55% (11/20) of the controls. Although the sEPSC amplitude of the two groups was similar, the sEPSC frequency in the kainate group was considerably higher than in the controls. The sEPSC frequency, but not amplitude, in kainate-treated animals was correlated with their seizure frequency. Local excitatory interactions between CA1 pyramidal neurons were detected with focal photolysis of caged glutamate in 31% (12/39) of neurons from epileptic animals, but only in 1 of 20 neurons (5%) from the control group. Within the kainate group, the rats that showed excitatory synaptic interactions had a higher sEPSC frequency than those rats that did not. Those rats with excitatory interactions also had a higher seizure rate.
CONCLUSIONS: Rats with kainate-induced epilepsy exhibited enhanced sEPSCs and increased connectivity among hippocampal CA1 neurons, which suggests that the formation of new local excitatory circuits was associated with recurrent seizures.