Glutamate receptor activation in the kindled dentate gyrus.
OBJECTIVE
The contribution of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-D-aspartate (NMDA), and kainate receptor activation to the enhanced seizure susceptibility of the dentate gyrus was investigated in an experimental model of temporal lobe epilepsy.


METHODS
Using the specific NMDA and AMPA receptor antagonists D-APV and SYM 2206, we examined alterations in glutamate receptor-dependent synaptic currents 48 hours and 28 days after kindling in field-potential and voltage-clamp recordings.


RESULTS
Forty-eight hours after kindling, the fractions of AMPA and NMDA receptor-mediated excitatory postsynaptic current components shifted dramatically in favor of the NMDA receptor-mediated response. Four weeks after kindling, however, AMPA and NMDA receptor-mediated excitatory postsynaptic currents reverted to control-like values. Neither single nor repetitive perforant path stimuli evoked kainate receptor-mediated excitatory postsynaptic currents in dentate gyrus granule cells of control or kindled rats.


CONCLUSIONS
The enhanced excitability of the kindled dentate gyrus 48 hours after the last seizure most likely results from transiently enhanced NMDA receptor activation. The NMDA receptor seems to play a critical role in the induction of the kindled state rather than in the persistence of the enhanced seizure susceptibility.
Behr
J
J
Department of Neurology, Reed Neurological Research Center, UCLA School of Medicine, Los Angeles, California 90095-1769, USA.
Heinemann
U
U
Mody
I
I
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D018891:Dentate Gyrus / Q000187:drug effects / Q000503:physiopathology*; D018728:Entorhinal Cortex / Q000502:physiology; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D007608:Kainic Acid / Q000494:pharmacology; D007696:Kindling, Neurologic / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D015763:2-Amino-5-phosphonovalerate; D007608:Kainic Acid; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate