NMDA receptor blockade prevents the increase in protein kinase C substrate (protein F1) phosphorylation produced by long-term potentiation

David J. Linden, Ka L. Wong, Fwu Shan Sheu, Aryeh Routtenberg*

*Corresponding author for this work

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Recent evidence has implicated activation of the N-methyl-d-aspartate (NMDA) class of glutamate receptor in the initiation of hippocampal long-term potentiation (LTP), an electrophysiological model of information storage in the brain. A separate line of evidence has suggested that activation of protein kinase C (PKC) and the consequent phosphorylation of it substrates is necessary for the maintenance of the LTP response. To determine if PKC activation is a consequence of NMDA receptor activation during LTP, we applied the NMDA receptor antagonist drug, dl-aminophosphonovalerate (APV) both immediately prior to and following high frequency stimulation, resulting in successful and unsuccessful blockade of LTP initiation, respectively. We then measured the phosphorylation of a PKC substrate (protein F1) in hippocampal tissue dissected from these animals. Only successful blockade of LTP initiation by prior application of APV was seen to block the LTP-associated increase in protein F1 phosphorylation measured in vitro (P < 0.0001 by ANOVA). This suggests that NMDA receptor-mediated initiation triggers maintenance processes that are, at least in part, mediated by protein F1 phosphorylation. These data provide the first evidence linking two mechanisms associated with LTP, NMDA receptor activation and PKC substrate phosphorylation.

Original languageEnglish (US)
Pages (from-to)142-146
Number of pages5
JournalBrain research
Volume458
Issue number1
DOIs
StatePublished - Aug 16 1988

Keywords

  • Long-term potentiation
  • N-Methyl-d-aspartate
  • Protein F1
  • Protein kinase C

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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