Behavioral stress modifies hippocampal synaptic plasticity through corticosterone-induced sustained extracellular signal-regulated kinase/mitogen-activated protein kinase activation

Chih Hao Yang, Chiung Chun Huang, Kuei Sen Hsu

Research output: Contribution to journalArticle

139 Citations (Scopus)

Abstract

The induction of hippocampal long-term synaptic plasticity is exquisitely sensitive to behavioral stress, but the underlying mechanisms are still unclear. We report here that hippocampal slices prepared from adult rats that had experienced unpredictable and inescapable restraint tail-shock stress showed marked impairments of long-term potentiation (LTP) in the CA1 region. The same stress promoted the induction of long-term depression (LTD). These effects were prevented when the animals were given the glucocorticoid receptor antagonist 11β,17β-11[4-(dimethylamino)phenyl]-17-hydroxy-17-(1-propynyl) -estra-4-9-dien-3-one before the stress. Immunoblotting analyses revealed that stress induced a profound and prolonged extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK1/2 MAPK) hyperphosphorylation through small GTPase Ras, Raf-1, and MAPK kinase 1/2 (MEK1/2). Furthermore, the stress effects were obviated by the intrahippocampal injection of specific inhibitors of MEK1/2 (U0126), protein kinase C (bisindolylmaleimide I), tyrosine kinase (K252a), and BDNF antisense oligonucleotides. These results suggest that the effects of stress on LTP and LTD originate from the corticosterone-induced sustained activation of ERK1/2-coupled signaling cascades.

Original languageEnglish
Pages (from-to)11029-11034
Number of pages6
JournalJournal of Neuroscience
Volume24
Issue number49
DOIs
Publication statusPublished - Dec 8 2004
Externally publishedYes

Keywords

  • Extracellular signal-related kinase
  • Glucocorticoid receptor
  • Hippocampus
  • Long-term depression
  • Long-term potentiation
  • Mitogen-activated protein kinase
  • Stress

ASJC Scopus subject areas

  • Neuroscience(all)

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