Electrophysiological correlates of seizure sensitivity in the dentate gyrus of epileptic juvenile and adult gerbils

Abstract

1. Naturally occurring inherited epilepsy is common among Mongolian gerbils, providing an opportunity to identify neurological factors that correlate with seizure behavior. In the present study we examine the ontogeny of seizure behavior and compare the electrophysiology and anatomy of the dentate gyrus in epileptic and nonepileptic gerbils. 2. Behavioral seizure testing revealed that young gerbils do not begin having seizures until they are 2 mo of age, at which time seizure incidence across animals is at its highest level. Most seizure-positive juvenile gerbils became epileptic adults, but 30% outgrew their epileptic condition. 3. The number of somatostatin- and parvalbumin-immunoreactive neurons in the dentate gyrus and Ammon's horn was counted, with the use of quantitative stereological techniques, in juvenile and adult gerbils. No significant differences were detected between epileptic and nonepileptic groups. 4. In dentate gyrus field potential responses to perforant path stimulation, adult epileptic gerbils showed enhanced paired-pulse inhibition at short (30 ms) interstimulus intervals and enhanced facilitation at intermediate (70 ms) intervals compared with nonepileptic controls. These differences were most pronounced when stimuli were delivered at faster (1.0 Hz) rather than slower (0.1 Hz) rates. 5. Compared with seizure-negative juveniles, seizure-positive juveniles showed the same pattern of paired-pulse response abnormalities as epileptic adults. However, seizure-positive juveniles had a lower threshold for maximal dentate activation than epileptic adults. 6. These results demonstrate similar functional abnormalities in the dentate gyri of epileptic adult gerbils and in juvenile gerbils before they experience multiple seizures. Such findings suggest that abnormalities in functional inhibition of the dentate gyrus network precede and therefore might contribute to overt seizure activity.