Protein phosphatase-mediated regulation of protein kinase C during long-term depression in the adult hippocampus in vivo

E. Thiels, B. I. Kanterewicz, L. T. Knapp, G. Barrionuevo, E. Klann

Research output: Contribution to journalArticlepeer-review


The neural substrates of learning and memory are thought to involve use-dependent long-term changes in synaptic function, including long-term depression (LTD) of synaptic strength. One biochemical event hypothesized to contribute to the maintenance and expression of LTD is decreased protein phosphorylation, caused by a decrease in protein kinase activity and/or an increase in protein phosphatase activity. We tested whether the activity of protein kinase C (PKC) decreases after the induction of LTD in area CA1 of the adult hippocampus in vivo, and then investigated the mechanism responsible for the LTD-associated alteration in PKC activity. We found that LTD was associated with a significant decrease in both autonomous and cofactordependent PKC activity. The decrease in PKC activity was prevented by NMDA receptor blockade and was not accompanied by a decrease in the level of either PKCα, β, γ, or ζ. Western blot analysis with phosphospecific antibodies revealed that phosphorylation of Ser-657 on the catalytic domain of PKCα (Ser-660 on PKCβII) was decreased significantly after the induction of LTD, and that this dephosphorylation was prevented by the protein phosphatase inhibitor okadaic acid. The decrease in autonomous and cofactor-dependent PKC activity likewise was prevented by okadaic acid. These findings suggest that LTD in the adult hippocampus in vivo involves a decrease in PKC activity that is mediated, at least in part, by dephosphorylation of the catalytic domain of PKC by protein phosphatases activated after LTD-inducing stimulation. Our findings are consistent with the idea that protein dephosphorylation contributes to the expression of LTD.

Original languageEnglish (US)
Pages (from-to)7199-7207
Number of pages9
JournalJournal of Neuroscience
Issue number19
StatePublished - Oct 1 2000


  • Area CA1
  • Dephosphorylation
  • Learning and memory
  • Long-term depression
  • Protein kinase C
  • Protein phosphatase

ASJC Scopus subject areas

  • General Medicine


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