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 language | English |
|---|---|
| Pages (from-to) | 409-417 |
| Number of pages | 9 |
| Journal | Journal of Biomedical Science |
| Volume | 6 |
| Issue number | 6 |
| Publication status | Published - Nov 1999 |
| Externally published | Yes |
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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)
Cite this
Involvement of mitogen-activated protein kinase in hippocampal long-term potentiation. / Wu, Shang Peng; Lu, Kwok Tung; Chang, Wen Chang; Gean, Po Wu.
In: Journal of Biomedical Science, Vol. 6, No. 6, 11.1999, p. 409-417.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Involvement of mitogen-activated protein kinase in hippocampal long-term potentiation
AU - Wu, Shang Peng
AU - Lu, Kwok Tung
AU - Chang, Wen Chang
AU - Gean, Po Wu
PY - 1999/11
Y1 - 1999/11
N2 - 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.
AB - 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.
KW - cAMP
KW - Forskolin
KW - Hippocampus
KW - Learning
KW - Memory
KW - Mitogen- activated
KW - Potentiation, long-term
KW - Protein kinase
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M3 - Article
VL - 6
SP - 409
EP - 417
JO - Journal of Biomedical Science
JF - Journal of Biomedical Science
SN - 1021-7770
IS - 6
ER -