TETANUS TOXIN-INDUCED SEIZURES IN INFANT RATS AND THEIR EFFECTS ON HIPPOCAMPAL EXCITABILITY IN ADULTHOOD

A new experimental model of developmental epilepsy is reported. Behavi oral and EEG features of seizures produced by unilateral intrahippocam pal injection of tetanus toxin in postnatal day 9-11 rats, are describ ed. Within 24-72 h of tetanus toxin injection, rat pups developed freq uent and often prolonged seizures which included combinations of repet itive wet dog shakes, and wild running-jumping seizures. Intrahippocam pal and cortical surface EEG recordings showed that coincident with th ese behaviors, electrographic seizures occurred not only in the inject ed hippocampus, but also in the contralateral hippocampus and bilatera lly in the neocortex. Analysis of the interictal EEG revealed multiple independent spike foci. One week following tetanus toxin injection, t he number of seizures markedly decreased; however, interictal spiking persisted. After injection rats were allowed to mature some were obser ved to have unprovoked behavioral seizures and/or epileptiform EEG act ivity. Mature animals were also studied using in vitro slice technique s. Recordings from hippocampal slices demonstrated spontaneous epilept iform burst discharges in the majority of rats which had tetanus toxin induced seizures as infants. These events occurred in area CA3 and co nsisted of interictal spikes and intracellularly recorded paroxysmal d epolarization shifts (PDSs). On rarer occasions, electrographic seizur es were recorded. The use of the tetanus toxin model in developing rat s may facilitate a better understanding of the unique features of epil eptogenesis in the developing brain and the consequences early-life se izures have on brain maturation and the genesis of epileptic condition s in later life.