Synaptic and axonal remodeling of mossy fibers in the hilus and supragranular region of the dentate gyrus in kainate-treated rats.

Abstract

Seizures evoked by kainic acid and a variety of experimental methods induce sprouting of the mossy fiber pathway in the dentate gyrus. In this study, the morphological features and spatial distribution of sprouted mossy fiber axons in the dorsal dentate gyrus of kainate-treated rats were directly shown in granule cells filled in vitro with biocytin and in vivo with the anterograde lectin tracer Phaseolus vulgaris leucoagglutinin (PHAL). Sprouted axon collaterals of biocytin-filled granule cells projected from the hilus of the dentate gyrus into the supragranular layer in both transverse and longitudinal directions in kainate-treated rats but were not observed in normal rats. The sprouted axon collaterals projected into the supragranular region for 600-700 microm along the septotemporal axis. Collaterals from granule cells in the infrapyramidal blade crossed the hilus and sprouted into the supragranular layer of the suprapyramidal blade. Sprouted axon segments in the supragranular layer had more terminal boutons per unit length than the axon segments in the hilus of both normal and kainate-treated rats but did not form giant boutons, which are characteristic of mossy fiber axons in the hilus and CA3. Mossy fiber axons in the hilus of kainate-treated rats had more small terminal boutons, fewer giant boutons, and there was a trend toward greater axon length compared with mossy fibers in the hilus of normal rats. With the additional length of supragranular sprouted collaterals, there was an overall increase in the length of mossy fiber axons in kainate-treated rats. The synaptic and axonal remodeling of the mossy fiber pathway could alter the functional properties of hippocampal circuitry by altering synaptic connectivity in local circuits within the hilus of the dentate gyrus and by increasing the divergence of the mossy fiber terminal field along the septotemporal axis.