Kindling-induced potentiation of excitatory and inhibitory inputs to hippocampal dentate granule cells. I. Effects on linear and non-linear response characteristics.

Epileptiform activity is known to alter both excitatory and inhibitory circuits within the network of neurons that comprise the hippocampal formation. In the present experiment, kindling-induced alterations in the functional properties of the rabbit perforant path-dentate circuit were analyzed using non-linear system analytic procedures. System input consisted of a random train of impulses applied to the perforant path. System output was the perforant path-granule cell population spike amplitude evoked by each impulse in the train. The results of non-linear systems analysis were compared with the results from twin impulse analysis of kindling-induced alterations within the hippocampal dentate gyrus. Compared to twin impulse procedures, non-linear systems analytic procedures revealed a reduced duration and magnitude of kindling-induced inhibitory interactions to interstimulus intervals of 10-200 ms. The increased magnitude of inhibitory interactions did not decay to prekindled magnitude until 16 weeks postkindling. In contrast, kindling-induced potentiation of the population spike had decayed within 10 weeks of the last stage 5 seizure. Despite the decay of electrophysiological responses to prekindled levels, only a few kindling stimulations were required to evoke fully kindled seizures. Thus, electrophysiological alterations within the first synaptic relay of the hippocampal trisynaptic circuit, the dentate gyrus, cannot explain the long duration of the kindling effect.