RESIDUAL GRANULE CELLS CAN MAINTAIN SUSCEPTIBILITY OF CA3 PYRAMIDAL CELLS TO KAINATE-INDUCED EPILEPTIFORM DISCHARGES

Slices of adult rat hippocampus made from animals exposed neonatally t o X-ray irradiation were studied with electrophysiological techniques. A single dose of 6 Gy irradiation of the pup's head significantly but unevenly reduced the number of granule cells in the dentate gyrus. A larger reduction was detected in the septal than in the temporal hippo campus. The number of hilar cells decreased also. Effects of irradiati on were confirmed with histological techniques. Field potential respon ses to mossy fiber stimulation in the pyramidal layer of the CA3 subfi eld was smaller in irradiated than in normal rats. Superfusion of the slices with kainic acid (KA, 300-500 nM) induced spontaneously recurre nt paroxysmal activity (SRPA) in about 40% of irradiated slices in con trast with nearly 90% of slices cut from nonirradiated rats. Intracell ular recordings from CA3 pyramidal cells in irradiated rats revealed r ecurrent bursts of action potentials on top of large depolarizing wave s after KA application. Cells impaled in slices from the septal half o f hippocampus of irradiated rats failed more often to respond with bur sts to KA than cells in slices cut from the temporal half. Removal of mossy fiber input can therefore reduce KA induced hyperexcitability of CA3 pyramidal cells, but quantitative factors such as proportional lo ss of granule and hilar cells may explain the considerable differences found among cells and slices. Removal of 80% of granule cells reduces hyperexcitability consistently, while SRPA can be found in slices whe re as much as 50% of granule cells are missing. Intracellular findings suggest that failures of detection of SRPA following KA application t o hippocampal slices of irradiated rats does not necessarily mean that CA3 pyramidal cells are no longer responding to KA with epileptiform bursting. (C) 1998 Wiley-Liss, Inc.