Abstracts

The elderly have the highest incidence and prevalence for seizure disorders with up to 50% of cases having no identifiable antecedent. Rodents also exhibit an aging-related increase in seizure susceptibility with aged rats having a higher frequency of wet-dog shakes and a shorter latency to onset for hippocampal-associated seizures and status epilepticus during kainate-treatment. Based on kainate[apos]s mode of action, we hypothesize that these differences reflect pro-convulsive changes in limbic circuitry. To test this hypothesis, electrophysiological recordings were performed in brain slices. The dentate gyrus was our model region since it is involved in generating wet-dog shakes and limbic seizures, and it is affected preferentially with age., Field potential and whole-cell recordings were used to assess dentate circuitry and function in brain slices from adult (3-8 mo.) and aged (22-32 mo.) Fischer 344 rats., No aging-related differences were noted in the maximal amplitude of orthodromic evoked field potential responses, or paired-pulse inhibition and facilitation (10 and 50 ms interpulse intervals). However, 5 Hz orthodromic stimulation (10 s) evoked multiple population spikes in 40% of aged slices (n = 10) vs. 0% of adult slices (n = 9; p = 0.033; chi-square). Further, when the dentate[apos]s capacity to filter 5 Hz afferent input was assessed by recording in CA3, approximately 30% of aged slices (n = 21) exhibited multiple spikes during the train which often progressed into spontaneous interictal-like events. Similar activity was not seen in adult slices (n = 16; p = 0.036; chi-square). Whole cell recordings revealed no aging-related differences in the membrane properties of granule cells within the linear portion of the IV curve (adult n = 22; aged n = 26), or the conductances and reversal potentials of the fast and slow IPSPs evoked with molecular layer stimulation (adult n = 17; aged n =21). In contrast, aged granule cells (n = 21) did exhibit a 50% reduction in the frequency of spontaneous IPSPs, compared to adults (n = 20; p [lt] 0.0001; ANOVA). Further, following disinhibition, aged granule cells (n = 16) had an increased probability for generating spontaneous large amplitude prolonged EPSPs (100-400 ms duration; [gt] 10 mV amplitude) compared to adult granule cells (n=18; p [lt] 0.05; ANOVA)., These data reveal that the capacity of the dentate gyrus to respond to and filter afferent input is altered in a pro-convulsive manner in aged rats. Further, these aging-related changes are associated with a compromise in inhibition and an increase in local excitatory activity. These changes could contribute to the enhanced susceptibility to wet-dog shakes and limbic seizures in aged rats during systemic kainate treatment and could contribute to the compromise in spatial learning and memory seen with age., (Supported by NIA and EFA.)