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 th e hippocampus is thought to require activation of N-methyl-D-aspartate rece ptors, an elevation of postsynaptic Ca2+ 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 L TD in the CA1 field of rat hippocampal slices. We show that LTD is associat ed with a transient (<30 min) and D-APS-sensitive reduction in GAP-43/B-50 and RC3 phosphorylation and that LTD is prevented by the phosphatase inhibi tors okadaic acid and cyclosporin A. Our data provide strong evidence for a transient increase in pre- and postsynaptic phosphatase activity during LT D. 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 Ca2+ signal and Ca2+/calmodu lin-dependent processes implicated in long term potentiation and LTD.