Analysis of Interictal-to-Ictal Transition in the Dentate Gyrus: Evidence for
Abstract number :
1.157
Submission category :
Year :
2000
Submission ID :
2863
Source :
www.aesnet.org
Presentation date :
12/2/2000 12:00:00 AM
Published date :
Dec 1, 2000, 06:00 AM
Authors :
Jennifer L Hellier, Peter R Patrylo, Ping Dou, Gregory M Rose, Kevin J Staley, F. Edward Dudek, U C H S C, Denver, CO; Yale Univ, New Haven, CT; Colorado State Univ, Fort Collins, CO; Memory Pharm, New York, NY.
RATIONALE: Although animal models of temporal lobe epilepsy have been used extensively for in vitro analyses of synaptic mechanisms, relatively few electrophysiological studies have used chronic recordings in freely behaving rats to analyze the mechanisms responsible for the interictal-to-ictal transition (i.e., the onset of spontaneous electrographic seizures). METHODS: Serial extracellular recordings from the dentate granule cell layer of the dorsal hippocampus were observed from rats with kainate-induced epilepsy (i.e., 1-11 months after kainate; n=18). Electrode stability was verified by the response to perforant path stimulation. RESULTS: Paired-pulse stimulation confirmed that inhibitory synaptic mechanisms were generally intact in the dentate gyrus of epileptic rats. Spontaneous interictal spikes had a variety of waveforms (e.g., spike-and-wave), but often appeared similar to field EPSPs with or without superimposed population spikes. Because these events resembled field EPSPs to perforant path stimulation and occurred in the presence of intact synaptic inhibition, they appeared to be due to excitatory synaptic input to the dentate. The onset of spontaneous electrographic seizures was associated with a progressive increase in the amplitude and frequency of interictal spikes, which resembled potentiation of field EPSPs. During the initial seconds of seizure onset, the field potentials developed population spikes that progressively increased in amplitude and number until individual events became unresolvable. Subsequent histological studies confirmed significant reorganization of the mossy fibers in all treated rats. CONCLUSIONS: These data suggest that interictal spikes in the dentate gyrus increase in frequency and amplitude at the onset of the electrographic seizure because of synchronous synaptic activation from an afferent network, such as entorhinal cortex or epileptic focus elsewhere in the reorganized dentate gyrus. This suggests that the dentate gyrus acts more as a gate than as a source of seizure initiation.