Excitotoxicity induced by enhanced excitatory neurotransmission in cultured hippocampal pyramidal neurons

April E. Abele*, Kenneth P. Scholz, Wendy K. Scholz, Richard J. Miller

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

132 Scopus citations

Abstract

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 ∼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, ∼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.

Original languageEnglish (US)
Pages (from-to)413-419
Number of pages7
JournalNeuron
Volume4
Issue number3
DOIs
StatePublished - Mar 1990

ASJC Scopus subject areas

  • Neuroscience(all)

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