In the guinea pig in vitro hippocampal slice preparation, we have demonstrated that the repeated tetanic stimulation of the Schaffer collateral-commissural input to CA1 pyramidal neurones produces a progressive increase in the amplitude and duration of postsynaptic potentials, and stimulus-induced and spontaneous paroxysmal depolarization shifts (PDSs). Both the enhancement of synaptic transmission and the genesis of PDSs were reversibly blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist (+/-)-2-amino-5-phosphonovalerate (APV). These results provide evidence that progressive, stimulation-induced long-term potentiation may serve as the trigger for kindling-induced epileptogenesis, and this process is dependent on the repeated activation of an APV-sensitive receptor.
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