Long-term depression in the adult hippocampus in vivo involves activation of extracellular signal-regulated kinase and phosphorylation of Elk-1

Edda Thiels, Beatriz I. Kanterewicz, Eric D. Norman, James M. Trzaskos, Eric Klann

Research output: Contribution to journalArticlepeer-review

Abstract

Protein kinase cascades likely play a critical role in the signaling events that underlie synaptic plasticity and memory. The extracellular signal-regulated kinase (E-RK) cascade is suited well for such a role because its targets include regulators of gene expression. Here we report that the ERK cascade is recruited during long-term depression (LTD) of synaptic strength in area CA1 of the adult hippocampus in vivo and selectively impacts on phosphorylation of the nuclear transcription factor Elk-1. Using a combination of in vivo electrophysiology, biochemistry, pharmacology, and immunohistochemistry, we found the following: (1) ERK phosphorylation, including phosphorylation of nuclear ERK, and ERK phosphotransferase activity are increased markedly, albeit transiently, after the induction of NMDA receptor-dependent LTD at the commissural input to area CA1 pyramidal cells in the hippocampus of anesthetized adult rats; (2) LTD-inducing paired-pulse stimulation fails to produce lasting LTD in the presence of the ERK kinase inhibitor SL327, which suggests that ERK activation is necessary for the persistence of LTD; and (3) ERK activation during LTD results in increased phosphorylation of Elk-1 but not of the transcription factor cAMP response element-binding protein. Our findings indicate that the ERK cascade transduces signals from the synapse to the nucleus during LTD in hippocampal area CA1 in vivo, as it does during long-term potentiation in area CA1, but that the pattern of coupling of the ERK cascade to transcriptional regulators differs between the two forms of synaptic plasticity.

Original languageEnglish (US)
Pages (from-to)2054-2062
Number of pages9
JournalJournal of Neuroscience
Volume22
Issue number6
DOIs
StatePublished - Mar 15 2002

Keywords

  • Elk-1
  • Extracellular signal-regulated kinase
  • Long-term depression
  • Mitogen-activated protein kinase
  • NMDA
  • Protein phosphorylation
  • Transcription factors
  • cAMP response element-binding protein

ASJC Scopus subject areas

  • Neuroscience(all)

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