N-methyl-D-aspartate-induced long-term depression is associated with a decrease in postsynaptic protein kinase C substrate phosphorylation in rat hippocampal slices.
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.
van Dam
Els J M
EJ
Department of Pharmacology and Anatomy, Rudolf Magnus Institute for Neurosciences, University Medical Center Utrecht, P.O. Box 85060, 3508 AB Utrecht, The Netherlands.
Ruiter
Bert
B
Kamal
Amer
A
Ramakers
Geert M J
GM
Gispen
Willem Hendrik
WH
de Graan
Pierre N E
PN
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D019922:GAP-43 Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D051579:Neurogranin; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000201:enzymology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D002148:Calmodulin-Binding Proteins; D018691:Excitatory Amino Acid Antagonists; D019922:GAP-43 Protein; D009419:Nerve Tissue Proteins; C496651:Nrgn protein, rat; D016194:Receptors, N-Methyl-D-Aspartate; D051579:Neurogranin; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D011493:Protein Kinase C