Activation of N-methyl-D-aspartate receptors parallels changes in cellular and synaptic properties of dentate gyrus granule cells after kindling.

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1. The cellular and synaptic properties of rat dentate gyrus granule cells (GCs) were examined using intra-/extracellular and Ca2+-sensitive microelectrode recordings following epilepsy induced by kindling of the hippocampal commissures or amygdala. 2. The recordings were made in hippocampal slices prepared from sham-stimulated controls and animals that have received daily stimuli to reach stage IV-V of kindling. The average number of stimulation trials (60 Hz/1 s, 100-150 microA) required to reach full motor seizures (stage V) was 23 +/- 2 for commissural kindling and 14 +/- 1 for amygdala kindling. 3. The resting membrane potential of GCs following kindling (RMP; -72 +/- 3 mV) was not significantly different from the RMP of control GCs (-70 +/- 2 mV). Similarly, action potential height and threshold were unaffected by kindling. However, kindling altered other cellular properties of GCs regardless of the site of stimulation (hippocampal commissures or amygdala), the stage of kindling reached (IV or V), or the time elapsed between the last kindling stimulus and preparation of the hippocampal slices (24 h-6 wk). The input resistance of kindled GCs (55 +/- 4 M omega) was significantly higher than that of controls (40 +/- 3 M omega). In contrast to most control GCs, the slope conductance (GS) of kindled neurons, measured with constant-amplitude current injections at various membrane potentials, generally increased at membrane potentials more negative than rest. Furthermore, other voltage-dependent ionic conductances (see below), that were not normally encountered in control GCs, were present in kindled neurons. 4. The intracellularly recorded monosynaptic excitatory postsynaptic potentials (EPSPs) of kindled GCs, evoked through the stimulation of the lateral perforant pathway, differed significantly from the EPSPs of control GCs. The amplitudes of control EPSPs increased upon hyperpolarizations and decreased following depolarizations of the membrane, as expected for conventional EPSPs without contribution from voltage-dependent conductances. In contrast, the EPSPs of kindled GCs invariably increased in amplitude and duration at membrane potentials 5-20 mV depolarized from rest, indicating the presence of a characteristic voltage-dependent component. Frequently, following the synaptically triggered action potentials, kindled GCs displayed depolarizing afterpotentials. 5. Perfusion of the N-methyl-D-aspartate (NMDA) receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV; 30 microM) had no effect on the EPSPs of control GCs, but consistently reduced the amplitude and duration of EPSPs in kindled GCs.(ABSTRACT TRUNCATED AT 400 WORDS)