Mossy fiber synaptic reorganization induced by kindling: time course of development, progression, and permanence

Abstract

Recent studies have revealed that mossy fiber axons of granule cells in the dentate gyrus undergo reorganization of their terminal projections in both animal models of epilepsy and human epilepsy. This synaptic reorganization has been demonstrated by the Timm method, a histochemical technique that selectively labels synaptic terminals of mossy fibers because of their high zinc content. It has been generally presumed that the reorganization of the terminal projections of the mossy fiber pathway is a consequence of axonal sprouting and synaptogenesis by mossy fibers. To evaluate this possibility further, the time course for development of Timm granules, which correspond ultrastructurally to mossy fiber synaptic terminals, was examined in the supragranular layer of the dentate gyrus at the initiation of kindling stimulation with an improved scoring method for assessment of alterations in Timm histochemistry. The progression and permanence of this histological alteration were similarly evaluated during the behavioral and electrographic evolution of kindling evoked by perforant path, amygdala, or olfactory bulb stimulation. Mossy fiber synaptic terminals developed in the supragranular region of the dentate gyrus by 4 d after initiation of kindling stimulation in a time course compatible with axon sprouting. The induced alterations in the terminal projections of the mossy fiber pathway progressed with the evolution of behavioral kindled seizures, became permanent in parallel with the development of longlasting susceptibility to evoked seizures, and were observed as long as 8 months after the last evoked kindled seizure. The results demonstrated a strong correlation between mossy fiber synaptic reorganization and the development, progression, and permanence of the kindling phenomenon.

Asymmetric accumulation of hippocampal 7S SNARE complexes occurs regardless of kindling paradigm

“…Based on these data, it would appear that accumulation of 7S SNARE complexes does correlate with a stable, kindling-induced, epileptic state. Amygdalar and entorhinal kindling has been associated with hippocampal mossy fiber sprouting and dentate granule cell neuronal loss (Cavazos et al, 1991). (Osawa et al, 2001) have demonstrated that in the case of amygdalar stimulation, kindling develops without evidence of mossy fiber sprouting until after repeated kindled convulsions, following death of granule cells in the dentate gyrus.…”

Kainate receptors in hippocampal CA3 subregion: evidence for a role in regulating neurotransmitter release

“…The kindling model of experimental epileptogenesis involves the generation of spontaneous seizures together with reorganization of mossy fiber synapses (McNamara, 1988;Sutula et al, 1988;Ben-Ari and Represa, 1990;Cavazos et al, 1991). It is interesting that together with synaptic reorganization of mossy fiber projections there appeared new [3H]kainate binding sites in the infrapyramidal cell layer of the CA3 subregion (Ben-Ari and Represa, 1990).…”

Matrix Metalloproteinase-9 Contributes to Kindled Seizure Development in Pentylenetetrazole-Treated Mice by Converting Pro-BDNF to Mature BDNF in the Hippocampus

“…Once established, kindling results in a permanent state of seizure susceptibility, which may manifest as spontaneous epileptiform seizures (Pinel and Rovner, 1978). Kindling has recently been shown to induce a variety of permanent structural changes in the brain, including sprouting of the mossy fiber pathway that originates from hippocampal dentate gyrus (DG) granule cells (Sutula et al, 1988;Cavazos et al, 1991) and neuronal loss in the hippocampus (Cavazos et al, 1994).…”