Excitotoxicity induced by enhanced excitatory neurotransmission in cultured hippocampal pyramidal neurons

Neuron. 1990 Mar;4(3):413-9. doi: 10.1016/0896-6273(90)90053-i.


Cultures of rat hippocampal pyramidal neurons were used to examine the roles of excitatory synaptic transmission, NMDA receptors, and elevated [Ca2+]i in the production of excitotoxicity. In integral of 70% of the cells observed, perfusion with Mg2(+)-free, glycine-supplemented medium induced large spontaneous fluctuations or maintained plateaus of [Ca2+]i. [Ca2+]i fluctuations could be blocked by tetrodotoxin, NMDA receptor antagonists, dihydropyridines, or compounds that inhibit synaptic transmission in the hippocampus, but not by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione. When cells were treated with Mg2(+)-free, glycine-supplemented medium and examined 24 hr later, integral of 30% of the neurons were found to have died. Cell death could be inhibited by the same agents that reduced [Ca2+]i fluctuations. These results support a role for direct excitatory synaptic transmission, as opposed to the general release of glutamate, in excitotoxicity. A major role for synaptically activated NMDA receptors, rather than kainate/quisqualate receptors, is also indicated. Neuronal death may be produced by abnormal changes in neuronal [Ca2+]i.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • Animals
  • Benzofurans
  • Calcium / metabolism
  • Cell Survival
  • Cells, Cultured
  • Electrophysiology / methods
  • Fluorescent Dyes
  • Fura-2
  • Glycine / pharmacology
  • Hippocampus / physiology*
  • Magnesium / pharmacology
  • Neurons / drug effects
  • Neurons / physiology*
  • Nimodipine / pharmacology
  • Pyramidal Tracts / physiology*
  • Quinoxalines / pharmacology
  • Rats
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter / drug effects
  • Receptors, Neurotransmitter / physiology
  • Synapses / drug effects
  • Synapses / physiology


  • Benzofurans
  • Fluorescent Dyes
  • Quinoxalines
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter
  • Nimodipine
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • Magnesium
  • Calcium
  • Glycine
  • Fura-2