DISTRIBUTION OF AMPA RECEPTOR SUBUNITS IN THE HIPPOCAMPAL-FORMATION OF TEMPORAL-LOBE EPILEPSY PATIENTS

The immunocytochemical distribution of the AMPA-selective receptor sub units GluR1 and GluR2/3 were mapped in the human hippocampal formation obtained from surgery for medically intractable temporal lobe epileps y. GluR2/3 immunoreactivity was detected in all principal cell types o f the hippocampal formation, including hilar neurons, granule cells of the dentate gyrus, and pyramidal cells of the cornu ammonis fields an d subiculum. GluR2/3 immunostaining typically filled the cell bodies a nd processes of neurons. A comparison of GluR2/3 immunoreactivity in a sclerotic specimen versus a non-sclerotic specimen demonstrated a pro found loss of staining, specifically in the areas where neuronal dropo ut was occurring, including CA1, CA3 and the hilus. An analysis of Glu R1 immunoreactivity in non-sclerotic specimens revealed that it was pr edominantly localized to cellular processes throughout the cornu ammon is fields, with a sparse staining of the dentate gyrus outer molecular layer and little to no staining of the dentate gyrus inner molecular layer. Similar to the GluR2/3-immunostained patterns, GluR1 immunoreac tivity was lost in the cornu ammonis fields of sclerotic hippocampal s pecimens, corresponding to patterns of neuronal dropout. Our most comp elling finding was a unique extensive pattern of GluR1 and GluR2/3 imm unoreactivity throughout the molecular layers of the dentate gyrus of severely compromised hippocampi. The altered staining of GluR1 and Glu R2/3 complements some of the patterns of axonal sprouting already desc ribed for the dentate gyrus, with a conjecture that their anatomy and distribution pattern underlies to some degree the reorganization of th e sclerotic hippocampus. A combination of enhanced glutamatergic trans mission and changes in neuropeptides that modulate hippocampal circuit ry could greatly affect the degree of excitability in the hippocampal formation. The alterations of GluR1 and GluR2/3 immunoreactivity in th e dentate gyrus add another component to the concept of reorganization in the epileptic sclerotic hippocampus.