Extracellular signal-regulated protein kinase activation is required for metabotropic glutamate receptor-dependent long-term depression in hippocampal area CA1

Sean M. Gallagher, Christine A. Daly, Mark F. Bear, Kimberly M. Huber

Research output: Contribution to journalArticle

194 Scopus citations

Abstract

Activation of group 1 metabotropic glutamate receptors (mGluRs) induces long-term depression (LTD) of synaptic transmission that relies on dendritic protein synthesis. We investigated the signal transduction pathways required for mGluR-LTD to identify candidate mechanisms for mGluR regulation of synaptic protein synthesis. Our results demonstrate a role for extracellular signal-regulated protein kinase (ERK), a subclass of the mitogen-activated protein kinases (MAPKs), in mGluR-LTD in area CA1 of the rat hippocampus. Inhibitors of the upstream kinase of ERK, MAP/ERK kinase significantly reduce mGluR-LTD induced by the group 1 agonist dihydroxyphenylglycine (DHPG) and synaptic stimulation but do not affect NMDA receptor-dependent LTD. In contrast, inhibitors of p38 MAPK were ineffective against DHPG-induced LTD. Consistent with the role of ERK in mGluR-LTD, we observed that DHPG treatment of hippocampal slices (isolated CA1), at concentrations that induce LTD, results in a robust phosphorylation of ERK but not of p38 MAPK. These results point to ERK as an important regulator of mGluR-LTD and a potential mechanism for mGluR regulation of synaptic protein synthesis.

Original languageEnglish (US)
Pages (from-to)4859-4864
Number of pages6
JournalJournal of Neuroscience
Volume24
Issue number20
DOIs
StatePublished - May 19 2004

Keywords

  • CA1
  • ERK
  • Hippocampus
  • Long-term depression
  • Metabotropic glutamate receptor
  • p38 MAPK

ASJC Scopus subject areas

  • Neuroscience(all)

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