Involvement of mitogen-activated protein kinase in hippocampal long-term potentiation

Shang Peng Wu, Kwok Tung Lu, Wen Chang Chang, Po Wu Gean

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31 Citations (Scopus)

Abstract

Mitogen-activated protein kinase (MAPK) cascade classically is thought to be involved in cellular transformation, including proliferation and differentiation. Recent behavioral studies suggest that MAPK may also have a role in learning and memory. Long-term potentiation (LTP), a candidate mechanism for learning and memory, has at least two distinct temporal phases: an early phase (E-LTP) which lasts for 1-2 h and a late phase (L-LTP) which can persist ≥3 h. Here, we report that PD 098059, a selective inhibitor of MAPK cascade, attenuates L-LTP induced by bath application of forskolin without affecting basal synaptic transmission. This effect was mimicked by direct injection of animals with MAPK antisense oligonucleotide into the hippocampal CA1 region. MAPK activity measured by using a synthetic peptide corresponding to the sequence surrounding the major site of phosphorylation of the myelin-basic protein by MAPK was enhanced by forskolin. The same antisense treatment also completely inhibited the increased MAPK activity. These results demonstrate an involvement of MAPK in the induction of L-LTP in the hippocampal CA1 neurons.

Original languageEnglish
Pages (from-to)409-417
Number of pages9
JournalJournal of Biomedical Science
Volume6
Issue number6
Publication statusPublished - Nov 1999
Externally publishedYes

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Keywords

  • cAMP
  • Forskolin
  • Hippocampus
  • Learning
  • Memory
  • Mitogen- activated
  • Potentiation, long-term
  • Protein kinase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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