The role of excitatory amino acid receptors in the propagation of epileptiform discharges from the entorhinal cortex to the dentate gyrus in vitro

Exp Brain Res. 1990;80(2):310-22. doi: 10.1007/BF00228158.

Abstract

The relationship between epileptiform events in the medial entorhinal cortex (MEC) and the dentate gyrus was investigated using a slice preparation from rat brain. Simultaneous intracellular recordings were made from neurones in layer II of the MEC and neurones in the granule cell layer of the dentate gyrus (DGC). Epileptiform activity was induced by perfusion with Mg+(+)-free medium or GABAA-receptor blockers. Epileptiform discharges in MEC cells were reflected on a one-to-one basis and at a latency of 1-3 ms by depolarizing events in DGC. The latter rarely gave rise to action potentials. Bath perfusion of the N-methyl-D-aspartate (NMDA) receptor blocker, 2-aminophosphonovalerate (2-AP5) abolished the Mg+(+)-free induced events in MEC cells and the corresponding depolarizations in the DGC but local application of 2-AP5 to the dentate gyrus only reduced the depolarizations. The non-NMDA-receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), whether bath applied or applied locally to the DG, had little effect on the cortical events but strongly reduced the depolarizations of the DGC. The discharges induced in MEC cells by GABA-blockers were reduced by bath applied 2-AP5 but abolished by CNQX. These effects were mirrored in the dentate gyrus by a reduction in the depolarizing events by 2-AP5 and their abolition by CNQX. Local application of either antagonist to the dentate gyrus reduced but did not abolish the depolarizations. Thus, Mg+(+)-free induced events in MEC depend mainly on enhanced NMDA-receptor activity, while events induced by bicuculline are primarily dependant on non-NMDA receptors. The depolarizing events in the DGC which reflect the activity in the EC are mediated by both types of receptor, although non-NMDA receptors play a much greater role.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • Action Potentials / drug effects
  • Animals
  • Bicuculline / pharmacology
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiopathology*
  • Epilepsy / chemically induced
  • Epilepsy / metabolism*
  • Epilepsy / physiopathology
  • Hippocampus / metabolism
  • Hippocampus / physiopathology*
  • In Vitro Techniques
  • Magnesium / physiology
  • Male
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Amino Acid
  • Receptors, Cell Surface / drug effects
  • Receptors, Cell Surface / physiology*
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter / drug effects
  • Receptors, Neurotransmitter / physiology*

Substances

  • Quinoxalines
  • Receptors, Amino Acid
  • Receptors, Cell Surface
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • 2-Amino-5-phosphonovalerate
  • Magnesium
  • Bicuculline