INCREASED DENSITIES OF AMPA GLUR1 SUBUNIT PROTEINS AND PRESYNAPTIC MOSSY FIBER SPROUTING IN THE FASCIA-DENTATA OF HUMAN HIPPOCAMPAL EPILEPSY

In human hippocampal epilepsy, there is a consistent pathology of cell loss and reactive synaptic reorganization of 'excitatory' mossy fiber s (MF) into the inner molecular layer (IML) of the fascia dentata (FD) . In this study, neo-Timm's histochemistry of MFs and immunocytochemis try of GluR1 were used to determine, in patients with or without hippo campal sclerosis (HS), if there was a correlation between aberrant sup ragranular (IML) mossy fiber sprouting and increased densities of AMPA GluR1 subunit proteins in the IML of the FD. Computerized quantified densitometric grey values of Timm and GluR1 densities were corrected f or the densities of granule cell losses using cell counts. In the LML of the HS group, despite the losses of granule cells, mossy fiber spro uting was significantly greater (P < 0.000001) and GluR1 protein densi ties were significantly higher(P < 0.0005) than those of the non-HS gr oup. Unlike supragranular mossy fiber sprouting, which was Limited to the IML, the increased GluR1 stainings were distributed throughout the whole molecular layer. For all cases, MF synaptic reorganization in t he supragranular ML was correlated with GluR1 subunit protein densitie s in the IML (R = 0.784, P < 0.0093). These data demonstrate that in t he human epileptic fascia dentata, there are significantly increased A MPA GluR1 subunit proteins associated with aberrant MF synaptic reorga nizations. This suggests that the hyperexcitability of sclerotic hippo campus occurs, at least in part, from the associated changes of both p resynaptic mossy fiber glutamatergic neoinnervation and increased GluR 1 subunit proteins in the dendritic domains of the FD. (C) 1998 Elsevi er Science B.V. All rights reserved.