HIPPOCAMPAL EEG EXCITABILITY AND CHRONIC SPONTANEOUS SEIZURES ARE ASSOCIATED WITH ABERRANT SYNAPTIC REORGANIZATION IN THE RAT INTRAHIPPOCAMPAL KAINATE MODEL

Previously, Mathern et al. (1992) demonstrated progressive mossy fiber (MF) sprouting in the intrahippocampal rat kainate seizure model. Thi s study looked at the time course of EEG hyperexcitability and spontan eous seizure activity in the same in vivo model to determine if seizur es were associated with MF sprouting. Results showed that animals prog ressed through 4 distinct EEG and behavioral phases and that in the ch ronic phase (greater than 90 days post kainate) MF sprouting was stron gly associated with hippocampal epileptogenesis. Progressive MF sprout ing into the inner molecular layer (IML) of the fascia dentata paralle led the EEG and behavioral appearance of independent hippocampal inter ictal epileptiform transients and chronic seizures. Hippocampi from ch ronic animals that demonstrated unilateral MF IML sprouting were obser ved to have interictal epileptiform transients and spontaneous seizure s that lateralized to the hippocampus with synaptically reorganized MF s. Chronic animals with bilateral MF sprouting were observed to have b ilateral independent EEG and behavioral hyperexcitability. Control ani mals and kainate treated animals that lacked hippocampal cell loss and MF sprouting did not show signs of chronic hippocampal EEG hyperexcit ability or chronic seizures. These data support the idea that MF sprou ting contributes to chronic hippocampal seizures by feedback excitatio n which leads to the excitability and synchronization required for a d amaged hippocampus to become an epileptic focus.