Blockers of NMDA receptor restore paired-pulse inhibition in the rat dentate gyrus lesioned by perforant path stimulation.
The ¿dormant basket cell' hypothesis postulates, that after status epilepticus, inhibitory interneurons in the hippocampus are deafferented from their excitatory inputs. We provide evidence for active suppression of hippocampal inhibition. Status epilepticus-like perforant path stimulation induced loss of interneurons and loss of inhibition in the rat dentate gyrus. This loss was transiently reversed by antagonists acting at three different sites of the N-methyl-d-aspartate (NMDA) receptor. Intrahippocampal administration of gamma-aminobutyric acid (GABA) agonists, which were expected to increase inhibition, resulted in the opposite effect. Although the substrate for the observed effects of pharmacological agents cannot be certainly confined to the ¿dormant' basket cell, they suggest the expression of hippocampal circuits that actively suppress inhibition through an NMDA synapse.
Mazarati
A M
AM
Department of Neurology, UCLA School of Medicine, USA. mazarati@ucla.edu
Wasterlain
C G
CG
D000818:Animals; D018891:Dentate Gyrus / Q000187:drug effects*; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005246:Feedback; D018682:GABA Agents / Q000494:pharmacology*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects*; D019580:Perforant Pathway / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D018691:Excitatory Amino Acid Antagonists; D018682:GABA Agents; D016194:Receptors, N-Methyl-D-Aspartate