Abstracts

Rationale: Genetic absence rat strains are resistant to generalization of kindling seizures induced by limbic stimulation. These observations raise the question whether the resistance is universal and independent of the stimulation site or whether it is related to the structures stimulated. Midline thalamic nuclei have been implicated as a critical region for the generalization of kindled limbic seizures. We compared kindling of the hippocampus and the midline thalamic nuclei in Sprague Dawley and WAG/Rij rats to determine whether kindling resistance was circuit specific. Methods: Following the implantation of a unilateral hippocampal, mediodorsal thalamus and frontal cortical electrodes, rats were kindled in either the hippocampus or midline thalamus until they were fully kindled or had received 50 stimulations. We evaluated the progression of the after discharge and behavioral seizure severity (Racine Scale). Results: Compared to Sprague-Dawley rats, the WAG/Rij animals with well developed spike wave discharges never fully kindled with hippocampal stimulation. In contrast both groups kindled rapidly with thalamic stimulation with many fewer stimulations compared to hippocampal stimulation. For the Sprague-Dawley rats, the mean number of stimulations for kindling was 21.6 4.15 (Mean SEM) for the hippocampus and 3.2 1.7 for the thalamus. In comparison WAG/Rij rats were not kindled after 50 stimulations but were kindled after 6.9 2.1 thalamic stimulations. Mean durations of the first thalamically induced afterdischarge were 15.1 1.7 and 12.1 1.5 seconds, respectively. Conclusions: Whereas WAG/Rijs are resistant to hippocampal kindling, they rapidly develop motor seizures with thalamic kindling. These findings suggest that resistance to generalization in WAG/Rij rats may arise from the inability to access networks for generalization from the limbic structures rather than complete resistance to generalization.