Abstracts

RATIONALE: The midline thalamic region has broad excitatory connections to the limbic sites involved in seizures, and other investigators have described that infusion of compounds into this area can prevent generalization of seizure activity in several models of limbic seizures. In this study we wished to determine whether infusion of proexcitatory compounds could alter the seizure activity itself.
METHODS: Rats were kindled under urethane anesthesia by stimulation in CA3 of one hippocampus, and seizures were recorded from contralateral CA1 and the medial dorsal thalamus. Drugs were infused into the midline thalamus with a cannula placed 0.3mm posterior to the thalamic recording electrode. 10 second, 20 Hz stimulus trains were given every 5 minutes until a stable afterdischarge duration was established. Drug was infused over 3-5 minutes and the change in afterdischarge duration was observed. An additional 10 stimulations after the infusion were given to determine the degree and duration of drug effect.
RESULTS: Bicuculline (300 fmol and 500 fmol, n=8 each dose) increased the afterdischarge duration significantly with a clear dose effect. Similarly glutamate (3 pmol, n=9), NMDA (150 fmol, n=9) and AMPA (100 fmol, n=6) significantly prolonged the duration of the afterdischarge (all p[lt]0.05). All effects were transient and lasted no longer than 10 minutes. Infusion of the drugs 3.0mm lateral to the midline infision site and infusion of saline into midline did not significantly alter electrographic seizure duration.
CONCLUSIONS: These findings suggest that the midline thalamic region may have a modulatory effect on limbic seizure activity, and may be a significant component of the limbic seizure circuitry.
Support: NIH grant NS-25605.