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 to 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 hippocampus. The number of hilar cells decreased also. Effects of irradiation were confirmed with histological techniques. Field potential responses to mossy fiber stimulation in the pyramidal layer of the CA3 subfield was smaller in irradiated than in normal rats. Superfusion of the slices with kainic acid (KA, 300-500 nM) induced spontaneously recurrent paroxysmal activity (SRPA) in about 40% of irradiated slices in contrast with nearly 90% of slices cut from nonirradiated rats. Intracellular recordings from CA3 pyramidal cells in irradiated rats revealed recurrent bursts of action potentials on top of large depolarizing waves after KA application. Cells impaled in slices from the septal half of hippocampus of irradiated rats failed more often to respond with bursts 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 loss 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 where as much as 50% of granule cells are missing. Intracellular findings suggest that failures of detection of SRPA following KA application to hippocampal slices of irradiated rats does not necessarily mean that CA3 pyramidal cells are no longer responding to KA with epileptiform bursting.
Czéh
B
B
Institute of Physiology, Medical University of Pécs, Hungary.
Seress
L
L
Czéh
G
G
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002452:Cell Count / Q000528:radiation effects; D004351:Drug Resistance; D004594:Electrophysiology; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D005110:Extracellular Space / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology / Q000528:radiation effects; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000502:physiology; D007608:Kainic Acid / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans
D007608:Kainic Acid