N-methyl-D-aspartate-induced long-term depression is associated with a decrease in postsynaptic protein kinase C substrate phosphorylation in rat hippocampal slices

Neurosci Lett. 2002 Mar 8;320(3):129-32. doi: 10.1016/s0304-3940(02)00037-x.

Abstract

Incubation of rat hippocampal slices with a low concentration of N-methyl-D-aspartate (NMDA; 20 microM; 3 min) elicits a form of long-term depression (LTD). We used this chemical protocol to study the involvement of pre- and postsynaptic protein kinase/phosphatase activity in NMDA receptor-dependent LTD. We determined the phosphorylation states of a pre- and a postsynaptic protein kinase C substrate, B-50/growth-associated protein 43 (GAP43) and RC3, respectively, using quantitative immunoprecipitation. NMDA incubation resulted in a 2-amino-5-phosphonovalerate-sensitive long-lasting (>60 min) decrease in synaptic efficacy and a concomitant reduction in RC3 phosphorylation. B-50/GAP43 phosphorylation was unaffected. This suggests that NMDA-LTD, in contrast to low frequency-LTD, is only associated with activation of postsynaptic protein phosphatases.

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • Animals
  • Calmodulin-Binding Proteins / metabolism*
  • Down-Regulation / drug effects
  • Down-Regulation / physiology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • GAP-43 Protein / metabolism
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / enzymology*
  • Male
  • N-Methylaspartate / pharmacology
  • Nerve Tissue Proteins / metabolism*
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Neurogranin
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Phosphorylation / drug effects
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / agonists
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Synapses / drug effects
  • Synapses / enzymology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*

Substances

  • Calmodulin-Binding Proteins
  • Excitatory Amino Acid Antagonists
  • GAP-43 Protein
  • Nerve Tissue Proteins
  • Nrgn protein, rat
  • Receptors, N-Methyl-D-Aspartate
  • Neurogranin
  • N-Methylaspartate
  • 2-Amino-5-phosphonovalerate
  • Protein Kinase C