Long term depression in the CA1 field is associated with a transient decrease in pre- and postsynaptic PKC substrate phosphorylation.
Induction of homosynaptic long term depression (LTD) in the CA1 field of the hippocampus is thought to require activation of N-methyl-d-aspartate receptors, an elevation of postsynaptic Ca(2+) levels, and a subsequent increase in phosphatase activity. To investigate the spatial and temporal changes in protein phosphatase activity following LTD induction, we determined the in situ phosphorylation state of a pre- (GAP-43/B-50) and postsynaptic (RC3) protein kinase C substrate during N-methyl-d-aspartate receptor-dependent LTD in the CA1 field of rat hippocampal slices. We show that LTD is associated with a transient (<30 min) and D-AP5-sensitive reduction in GAP-43/B-50 and RC3 phosphorylation and that LTD is prevented by the phosphatase inhibitors okadaic acid and cyclosporin A. Our data provide strong evidence for a transient increase in pre- and postsynaptic phosphatase activity during LTD. Since the in situ phosphorylation of the calmodulin-binding proteins GAP-43/B-50 and RC3 changes during both LTD and long term potentiation, these proteins may form part of the link between the Ca(2+) signal and Ca(2+)/calmodulin-dependent processes implicated in long term potentiation and LTD.
Ramakers
G M
GM
Rudolf Magnus Institute for Neurosciences, Department of Medical Pharmacology, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands. g.j.j.ramakers@med.uu.nl
Heinen
K
K
Gispen
W H
WH
de Graan
P N
PN
D000818:Animals; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D019922:GAP-43 Protein / Q000378:metabolism*; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051579:Neurogranin; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats
D002148:Calmodulin-Binding Proteins; D019922:GAP-43 Protein; D009419:Nerve Tissue Proteins; C496651:Nrgn protein, rat; D051579:Neurogranin; D011493:Protein Kinase C