Biochemical and morphological changes in the rat hippocampus following transection of the fimbria-fornix

Abstract

According to electrophysiological studies, the subcortically denervated hippocampus has been suggested as a model for limbic epilepsy. We investigated a) whether fimbrial lesioning leads to any biochemical or morphological changes in the rat hippocampus, b) if these changes give any explanation to the previously indicated hyperexcitability, and c) if the changes are in line with the findings in other experimental models and human epilepsy. The fimbria-fornix transection was done by aspiration. Four months later, spontaneous EEG activities were recorded, and the hippocampal formation was processed for histology. In addition, a separate group of lesioned rats was used for hippocampal amino acid analysis. Hyperexcitable functioning of the hippocampus was seen as frequent and rhythmic spiking activity in 25% of the fimbria-fornix-lesioned rats, although the rest of them had spikes occasionally. The amino acids analysis revealed a notable decrease in the concentration of GABA but no significant changes in the amount of excitatory amino acids. This suggests impaired GABAergic functioning but does not exclude possible abnormalities in the release of both excitatory and inhibitory amino acids. The number of somatostatin-immunoreactive (SOM-IR) neurons, a subpopulation of GABAergic neurons, was decreased in all the areas of the hippocampus (CA3 > CA1 > hilus), but this was statistically significant only in the CA3 area. Interestingly, it is the region from which interictal spiking activity in the subcortically denervated rat presumable originates. Immunostaining for synaptophysin showed a dense band of granules in the inner molecular layer of the dentate gyrus, indicating probable synaptic reorganization of associational afferents.