Long-lasting hippocampal plasticity in the kainic acid model of temporal lobe epilepsy

Seizures in temporal lobe epilepsy (TLE) often originate from the hippocampus. It is not known whether the physiological and structural changes in the hippocampal formation are the cause or the effect of seizures. In order to understand the long-lasting changes in the synaptic transmission and interactions in the hippocampus, evoked field potential mapping and current source density (CSD) analysis techniques were performed in control or kainate-treated rats in vivo in this thesis.; I began with studies on the synaptic interactions between CA3 and other regions of the hippocampus in normal rats. Stimulation of CA3 in urethane-anesthetized rats resulted in early excitation in the dentate gyrus (DG) as revealed by a short-latency sink at the inner molecular layer, likely mediated by direct associational fibers or via hilar mossy cells. CA3 stimulation also evoked a long-latency (≥20MS) sink at the middle molecular layer of the DG. CA3 stimulation evoked recurrent excitation within CA3. A differential activation of the basal and apical dendrites of CA1 was found following stimulation of CA3a or CA3b. Stimulation of the medial perforant path (MPP), a major input of entorhinal cortex (EC) to the hippocampus, resulted in mono- and poly-synaptic excitation in the DG, CA3 and CA1. These results suggested that information flow from EC to the hippocampus is not unidirectional as previously reported.; Increased mossy fiber sprouting (MFS) was found at two to four months after kainate seizures. However, the degree of MFS was negatively correlated with the inner molecular layer sink following CA3 stimulation. In addition, the paired-pulse inhibition was increased in the DG. The enhanced DG inhibition is "fragile" as revealed by bursting following a low dose of bicuculline (a GABAA receptor antagonist) that did not increase DG excitability in control rats.; Synaptic transmission in CA1 was differentially changed in different dendritic layers in KA-treated rats. A trisynaptic apical dendritic excitation following MPP stimulation was decreased, likely due to an increase in DG inhibition and CA3 cell loss after seizures. However, spike excitability in the basal and distal apical dendrites was increased, likely explained by a selective loss of interneurons, e.g. somatostatin-containing interneurons in CA1 in KA-treated rats.; Reverberant activity through the hippocampo-entorhinal loop was significantly enhanced in KA-treated as compared to control rats. CA3 stimulation resulted in long-latency population spikes in the DG and in CA1. The reverberant spike activity was likely mediated by direct MPP activation of the DG and CA1 respectively, after activation of CA3, CA1 and EC.; In summary, the synaptic interactions in the hippocampal and hippocampo-entorhinal circuits may regulate information processes in the normal and epileptic conditions. The fragile DG inhibition, the strengthening of direct EC to hippocampal inputs, increased CA1 dendritic excitation and enhanced reverberation through the hippocampo-entorhinal loop may all contribute to the increased seizure susceptibility in TLE.