Development of acquired temporal lobe epilepsy (TLE) is accompanied by selective cell loss and reorganization of excitatory synaptic circuits in key brain regions. Of particular research focus, the axons of granule cells in the dentate gyms (i.e., mossy fibers) have long been known to sprout collaterals and form new excitatory synapses with other granule cells after an epileptogenic insult. Thus, so-called "mossy fiber sprouting" (MFS) is associated with the formation of new, recurrent, excitatory circuits amongst granule cells, capable of supporting seizure-like activity in the dentate gyrus.The longstanding hypothesis that MFS and synaptic reorganization in the dentate gyrus serve as a potential substrate for seizure generation or propagation is intuitive and attractive to many research scientists. However, efforts to correlate the degree of MFS with seizure frequency have met with mixed results and more often than not have been inconclusive. Moreover, the loss of large numbers of hilar neurons and CA3 pyramidal cells-the typical targets of mossy fibers-during TLE acquisition complicate understanding of the functional significance of MFS as it relates to hippocampal excitability.
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