Abstracts

RATIONALE: The functional anatomy of limbic epilepsy is not well understood, but there is growing evidence that the midline thalamic nuclei, which have significant reciprocal connections with multiple limbic sites, may play a role in the primary seizure circuits as well as the process of seizure generalization. In this study we wished to determine if inhibition of neuronal activity in this region has an effect on the electrographic seizure activity or the behavioral accompaniment in animals with stable kindled seizures.
METHODS: Nine adult male Sprague-Dawley rats were implanted with a bipolar electrode in the mid ventral hippocampus. They also received a cannula guide that remained outside the dura. Following one week of recovery the animals were kindled with a modified rapid kindling protocol (one stimulation every hour, six stimulations per session, sessions separated by at least one day). Stimuli consisted of 2 second trains of 50 Hz biphasic, 1 ms square wave pulses at 600 microamps peak to peak. When the animals consistently had stage 5 motor seizures to each stimulation they were given either muscimol (MUS, 30nmol in 1 microliter) or tetrodotoxin (TTX, 60 pmol in 1 microliter) were injected via a cannula into the midline thalamic region 5 to 10 minutes before a stimulation. Behavioral seizure scores (Racine scale) and afterdischarge duration were measured and compared to baseline values.
RESULTS: All 4 of the TTX rats and 4 of the 5 MUS rats had a complete suppression of the motor seizure (reduced to scores of 1 or 2) and had shortening of the hippocampal afterdischarge. Following the injections the animals were behaviorally quiet, but able to ambulate when stimulated.
CONCLUSIONS: This study suggests that the midline thalamus is involved in the process of seizure generalization. In addition the associated reduction in afterdischarge duration suggests that this thalamic region is an integral part of the primary seizure circuit, and that modulation of the activity in this subcortical area will effect electrographic seizure activity in the limbic regions. The observation that there was no inhibition of spontaneous motor activity following the injections indicates that the suppression of limbic motor seizures was not the result of a direct inhibition of the motor system.
Objectives: At the conclusion of this presentation the participant will have a better understanding of the role of subcortical regions in limbic seizure activity.
[Supported by: NS-25605]