Abstracts

RATIONALE: Temporal lobe epilepsy which develops after febrile seizures often has progressive features and is associated with hippocampal sclerosis. Because this common epileptic syndrome following febrile seizures in childhood can be effectively treated or even cured by resection of the sclerotic hippocampus, febrile seizures during development may induce long-term abnormalities in hippocampal circuitry that promote abnormal excitability and susceptibility to epileptic synchronization in adulthood. To further define the regional specificity and age-dependence of long-term hippocampal alterations induced by febrile seizures that could contribute to temporal lobe epilepsy in adulthood, functional alterations in hippocampal circuitry were assessed by measuring paired pulse inhibition(PPI)in the dentate gyrus(DG)and CA3 of adult rats(~P95)that experienced febrile seizures during postnatal development. METHODS: PPI was assessed in the DG and CA3 in hippocampal slices of ~P95 rats that experienced seizures induced by hyperthermia on each of the following days: P4,P7,P10(Group I), P11,P14,P17(Group II), and P20,P23,P26(Group III). The ratio of the population spike evoked by a test and conditioning pulse at a standardized stimulus intensity delivered to the perforant path or the granule cell layer was compared in Groups I,II,III and age-matched controls. RESULTS: PPI at 15-25 ms interpulse intervals was increased in both the DG and CA3 of ~P95 rats after febrile seizures evoked during P4-P10, but was decreased in these regions after febrile seizures occurring during P20-P27. After febrile seizures experienced during P11-17, PPI was increased in the DG but was unchanged in CA3. CONCLUSIONS: The results demonstrated that febrile seizures during postnatal development in the rat induce regionally and temporally specific long-term functional alterations in hippocampal circuits. Febrile seizures during P20-P27 induced a long-term reduction in PPI in both the DG and CA3, an age-dependent alteration in the balance of excitation and inhibition that could promote epileptic synchronization in adulthood.