Group I metabotropic glutamate receptor inhibition selectively blocks a prolonged Ca2+ elevation associated with age-dependent excitotoxicity

G. V. Clodfelter, O. Thibault, J. Staton, P. W. Landfield, N. M. Porter

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


It has been recognized for some years that a prolonged Ca2+ elevation that is predictive of impending cell death develops in cultured neurons following excitotoxic insult. In addition, neurons exhibit enhanced sensitivity to excitotoxic insult with increasing age in culture. However, little is known about the processes that selectively regulate the post-insult Ca2+ elevation and therefore, it remains unclear whether it is associated specifically with age-dependent toxicity. Here, we tested the hypothesis that a group I metabotropic glutamate receptor antagonist selectively modulates the prolonged Ca2+ elevation in direct association with its protective effects against excitotoxicity. Rat hippocampal cultures of two ages (8-9 and 21-28 days in vitro) were exposed to a 5-min glutamate insult (400 μM in younger and 10 μM in older cultures) sufficient to kill >50% of the neurons, and were treated with vehicle or the specific group I metabotropic glutamate receptor antagonist 1-aminoindan-1,5-dicarboxylic acid (AIDA; 1 mM), throughout and following the insult. Neuronal survival was quantified 24 h after insult. In parallel studies, neurons of similar age in culture were imaged ratiometrically with a confocal microscope during and for 60 min after the glutamate insult. A large post-insult Ca2+ elevation was present in older but not most younger neurons. The N-methyl-D-aspartate receptor antagonist, MK-801, blocked the Ca2+ elevation both during and following the insult. In contrast, AIDA blocked only the post-insult prolonged Ca2+ elevation in older neurons. Moreover, AIDA was neuroprotective in older but not younger cultures. From these results we suggest that the post-insult Ca2+ elevation is regulated differently from the Ca2+ elevation during glutamate insult and is modulated by group I metabotropic glutamate receptors. Further, the prolonged Ca2+ elevation appears to be directly linked to an age-dependent component of vulnerability.

Original languageEnglish
Pages (from-to)183-194
Number of pages12
Issue number1
StatePublished - Jun 12 2002


  • AIDA
  • Aging
  • Cell culture
  • Hippocampus
  • NMDA
  • Neurotoxicity

ASJC Scopus subject areas

  • General Neuroscience


Dive into the research topics of 'Group I metabotropic glutamate receptor inhibition selectively blocks a prolonged Ca2+ elevation associated with age-dependent excitotoxicity'. Together they form a unique fingerprint.

Cite this