Optical recording study of granule cell activities in the hippocampal dentate gyrus of kainate-treated rats

Optical recording study of granule cell activities in the hippocampal denta te gyrus of kainate-treated rats. J. Neurophysiol. 83: 2421-2430, 2000. In the epileptic hippocampus, newly sprouted mossy fibers are considered to fo rm recurrent excitatory connections to granule cells in the dentate gyrus a nd thereby increase seizure susceptibility. To study the effects of mossy f iber sprouting on neural activity in individual lamellae of the dentate gyr us, we used high-speed optical recording to record signals from voltage-sen sitive dye in hippocampal slices prepared from kainate-treated epileptic ra ts (KA rats). In 14 of 24 slices from KA rats, hilar stimulation evoked a l arge depolarization in almost the entire molecular layer in which granule c ell apical dendrites are located. The signals were identified as postsynapt ic responses because of their dependence on extracellular Ca2+. The depolar ization amplitude was largest in the inner molecular layer (the target area of sprouted mossy fibers) and declined with increasing distance from the g ranule cell layer. In the inner molecular layer, a good correlation was obt ained between depolarization size and the density of mossy fiber terminals detected by Timm staining methods. Blockade of GABAergic inhibition by bicu culline enlarged the depolarization in granule cell dendrites. Our data ind icate that mossy fiber sprouting results in a large and prolonged synaptic depolarization in an extensive dendritic area and that the enhanced GABAerg ic inhibition partly masks the synaptic depolarization. However, despite th e large dendritic excitation induced by the sprouted mossy fibers, seizurel ike activity of granule cells was never observed, even when GABAergic inhib ition was blocked. Therefore, mossy fiber sprouting may not play a critical role in epileptogenesis.