Changes in excitatory neurotransmission in the CA1 region and dentate gyrus in a chronic model of temporal lobe epilepsy

E. W. Lothman, D. A. Rempe and P. S. Mangan Department of Neurology, University of Virginia Health Sciences Center, Charlottesville 22908, USA. 1. In this report we compare changes of excitatory neurotransmission within the CA1 region and the dentate gyrus (DG) in a model of chronic temporal lobe epilepsy (TLE). Extracellular and intracellular recordings were obtained from in vitro hippocampal-parahippocampal slices > or = 1 mo after a period of self-sustaining limbic status epilepticus (SSLSE) induced by continuous hippocampal stimulation. Pyramidal cells in CA1 were activated by electrodes in the stratum lacunosum/moleculare or stratum radiatum. Granule cells in DG were similarly activated by electrodes positioned in the perforant path. 2. Monosynaptic excitatory postsynaptic potentials (EPSPs) evoked in CA1 pyramidal cells in post-SSLSE tissue were always longer than those evoked in control tissue, irrespective of whether hyperresponsiveness was present or not. EPSPs elicited by stimulus subthreshold for action potentials (APs) in post-SSLSE and in control slices and matched in amplitude had a statistically greater duration in the post-SSLSE slices. Durations of monosynaptic EPSPs elicited by stimuli subthreshold for APs in DG granule cells in post-SSLSE slices were not longer than EPSPs of equal amplitude elicited in control slices. 3. Higher-intensity stimuli produced EPSPs with associated APs and, in certain cases in the post-SSLSE tissue, hyperresponsive events with multiple (> or = 3) APs. Durations of depolarizing profiles with stimuli producing APs were overall longer in both CA1 pyramidal cells and DG granule cells and correlated with the degree of hyperresponsiveness. 4. Neither the amplitudes nor the durations of monosynaptic EPSPs evoked in CA1 pyramidal cells in slices from control animals were affected by the addition of D(-)-2-amino-5-phosphonovaleric acid (APV), a blocker of the N-methyl-D-aspartate (NMDA) receptor, to the artificial cerebrospinal fluid (ACSF) bathing the slices. In contrast to the situation in control tissue, in post-SSLSE tissue APV shortened EPSPs evoked in CA1 pyramidal cells while not changing their amplitudes. After APV, inhibitory postsynaptic potentials (IPSPs) remained greatly diminished or absent in CA1 pyramidal cells. APV did not statistically decrease amplitudes of monosynaptic EPSPs evoked in DG granule cells in either control slices or post-SSLSE slices. APV decreased EPSP durations in both types of slices,