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The Journal of Neuroscience, May 15, 1998, 18(10):3589-3596
Evidence for Involvement of the cGMP-Protein Kinase G Signaling
System in the Induction of Long-Term Depression, But Not Long-Term
Potentiation, in the Dentate Gyrus In Vitro
Jianqun
Wu1,
Yue
Wang1,
Michael J.
Rowan2, and
Roger
Anwyl1
Departments of 1 Physiology and
2 Pharmacology and Therapeutics, Trinity College, Dublin 2, Ireland
The involvement of the cGMP-protein kinase G (PKG) signaling
pathway in the induction of long-term depression (LTD) and long-term potentiation (LTP) was investigated in the medial perforant path of the
dentate gyrus in vitro. Low-frequency stimulation
(LFS)-induced LTD of field EPSPs was inhibited by bath perfusion of the
selective soluble guanylyl cyclase inhibitor 1H-[1,2,4]
oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ). LFS-induced LTD of EPSPs
and whole-cell patch-clamped EPSCs was also blocked by bath perfusion
and postsynaptic intracellular injection, respectively, of the
selective PKG inhibitor KT5823. Elevation of intracellular cGMP by
perfusion of the cGMP phosphodiesterase inhibitor zaprinast resulted in
induction of LTD of field EPSPs and EPSCs. Occlusion experiments showed
mutual inhibition between LFS-induced LTD and zaprinast-induced LTD.
The zaprinast-induced LTD of field EPSPs was inhibited by perfusion
of ODQ and KT5823. In addition, zaprinast-induced LTD of EPSCs was
inhibited by postsynaptic application of KT5823. Glutamate receptor
stimulation, especially that of metabotropic glutamate receptors
(mGluRs), was required for zaprinast-induced LTD, because cessation of
test stimulation or perfusion with the mGluR antagonist
(+)- -methyl-4-carboxyphenylglycine (MCPG) inhibited
zaprinast-induced LTD. No inhibitory effect of ODQ or KT5823 on the
induction of LTP of EPSPs or EPSCs was found. These data indicate that
the cGMP-guanyly cyclase-PKG signaling pathway in the dentate gyrus
is essential for induction of LTD, although not of LTP, in the dentate
gyrus.
Key words:
long-term depression; hippocampus; cGMP; protein kinase
G; EPSP; long-term potentiation
Copyright © 1998 Society for Neuroscience 0270-6474/98/18103589-08$05.00/0
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