Long-term depression in the hippocampus in vivo is associated with protein phosphatase-dependent alterations in extracellular signal-regulated kinase

Eric D. Norman, Edda Thiels, German Barrionuevo, Eric Klann

Research output: Contribution to journalArticle

Abstract

There is growing evidence that activation of either protein kinases or protein phosphatases determines the type of plasticity observed after different patterns of hippocampal stimulation. Because activation of the extracellular signal-regulated kinase (ERK) has been shown to be necessary for long-term potentiation, we investigated the regulation of ERK in long- term depression (LTD) in the adult hippocampus in vivo. We found that ERK immunoreactivity was decreased following the induction of LTD and that this decrease required NMDA receptor activation. The LTD-associated decrease in ERK immunoreactivity could be simulated in vitro via incubation of either purified ERK2 or hippocampal homogenates with either protein phosphatase 1 or protein phosphatase 2A. The protein phosphatase-dependent decrease in ERK immunoreactivity was inhibited by microcystin. Intrahippocampal administration of the protein phosphatase inhibitor okadaic acid blocked the LTD-associated decrease in ERK2, but not ERK1, immunoreactivity. Collectively, these data demonstrate that protein phosphatases can decrease ERK immunoreactivity and that such a decrease occurs with ERK2 during LTD. These observations provide the first demonstration of a biochemical alteration of ERK in LTD.

Original languageEnglish (US)
Pages (from-to)192-198
Number of pages7
JournalJournal of Neurochemistry
Volume74
Issue number1
DOIs
StatePublished - 2000

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Phosphoprotein Phosphatases
Extracellular Signal-Regulated MAP Kinases
Hippocampus
Chemical activation
Protein Phosphatase 1
Protein Phosphatase 2
Okadaic Acid
Long-Term Potentiation
N-Methyl-D-Aspartate Receptors
Protein Kinases
Plasticity
Demonstrations

Keywords

  • Extracellular signal-regulated kinase
  • Hippocampus
  • Long-term depression
  • Plasticity
  • Protein phosphatase 1
  • Protein phosphatase 2A

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Long-term depression in the hippocampus in vivo is associated with protein phosphatase-dependent alterations in extracellular signal-regulated kinase. / Norman, Eric D.; Thiels, Edda; Barrionuevo, German; Klann, Eric.

In: Journal of Neurochemistry, Vol. 74, No. 1, 2000, p. 192-198.

Research output: Contribution to journalArticle

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