Abstract

In the kainate model of epilepsy, electrophysiological and anatomical modifications occur in inhibitory circuits of the CA1 region of the rat hippocampus. Using postembedding GABA immunocytochemistry and electron microscopy, we characterized perisomatic GABA and non-GABA synaptic contacts in CA1 pyramidal cells, and GABAergic interneurons of stratum oriens/alveus and stratum lacunosum-moleculare, and examined if changes occurred at these synapses at two weeks post-kainate treatment. We found that, in control rats, the number and total length of perisomatic GABA synapses were significantly smaller (approximately 40–50%) in lacunosum-moleculare interneurons than in oriens/alveus interneurons and pyramidal cells. Additionally, the number and total length of perisomatic non-GABA synapses were different among all cell types, with these parameters increasing significantly in the following order: pyramidal cells<lacunosum-moleculare interneurons<oriens/alveus interneurons. Following kainate treatment, we found that the number and total length of GABA synapses were significantly increased in lacunosum-moleculare interneurons (by 76% and 100%, respectively), but were unchanged in pyramidal cells and oriens/alveus interneurons. In addition, the mean length of individual GABA synapses was significantly increased (by 17%) in pyramidal cells after kainate treatment. In contrast, no changes were observed at non-GABA synapses in any cell type examined after kainate treatment. These results indicate that, in control animals, the ultrastructural correlates of perisomatic GABA inhibition are less pronounced in lacunosum-moleculare than oriens/alveus interneurons or pyramidal cells, whereas those of perisomatic excitation are more prominent in oriens/alveus than lacunosum-moleculare interneurons, and much less present in pyramidal cells. In addition, our results with kainate-treated animals suggest that cell-specific changes in perisomatic inhibition may occur in CA1 inhibitory interneurons in the chronically hyperexcitable hippocampus. The ultrastructural correlates of perisomatic inhibition were increased in lacunosum-moleculare interneurons, which may thus suggest some disinhibition of pyramidal cells. However, the ultrastructural correlates of perisomatic inhibition were increased in pyramidal cells, implying some enhancement of perisomatic inhibition of principal cells in the hyperexcitable hippocampus.

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