TY - JOUR
T1 - Role of guanylyl cyclase and cGMP-dependent protein kinase in long-term potentiation
AU - Zhuo, Min
AU - Hu, Yinghe
AU - Schultz, Carsten
AU - Kandel, Eric R.
AU - Hawkins, Robert D.
PY - 1994
Y1 - 1994
N2 - SEVERAL lines of evidence suggest that cyclic GMP might be involved in long-term potentiation (LTP) in the hippocampus1-6. Arachidonic acid, nitric oxide and carbon monoxide, three molecules that have been proposed to act as retrograde messengers in LTP7-9, all activate soluble guanylyl cyclase1,10,11. We report here that an inhibitor of guanylyl cyclase blocks the induction of LTP in the CA1 region of hippocampal slices. Conversely, cGMP analogues produce long-lasting enhancement of the excitatory postsyn-aptic potential if they are applied at the same time as weak tetanic stimulation of the presynaptic fibres. The enhancement is spatially restricted, is not blocked by valeric acid (APV), nifedipine, or picrotoxin, and partially occludes LTP. This synaptic enhancement may be mediated by the cGMP-dependent protein kinase (PKG). Inhibitors of PKG block the induction of LTP, and activators of PKG produce activity-dependent long-lasting enhancement. These results suggest that guanylyl cyclase and PKG contribute to LTP, possibly as activity-dependent presynaptic effectors of retrograde messengers.
AB - SEVERAL lines of evidence suggest that cyclic GMP might be involved in long-term potentiation (LTP) in the hippocampus1-6. Arachidonic acid, nitric oxide and carbon monoxide, three molecules that have been proposed to act as retrograde messengers in LTP7-9, all activate soluble guanylyl cyclase1,10,11. We report here that an inhibitor of guanylyl cyclase blocks the induction of LTP in the CA1 region of hippocampal slices. Conversely, cGMP analogues produce long-lasting enhancement of the excitatory postsyn-aptic potential if they are applied at the same time as weak tetanic stimulation of the presynaptic fibres. The enhancement is spatially restricted, is not blocked by valeric acid (APV), nifedipine, or picrotoxin, and partially occludes LTP. This synaptic enhancement may be mediated by the cGMP-dependent protein kinase (PKG). Inhibitors of PKG block the induction of LTP, and activators of PKG produce activity-dependent long-lasting enhancement. These results suggest that guanylyl cyclase and PKG contribute to LTP, possibly as activity-dependent presynaptic effectors of retrograde messengers.
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U2 - 10.1038/368635a0
DO - 10.1038/368635a0
M3 - Article
C2 - 7908417
AN - SCOPUS:0028275855
SN - 0028-0836
VL - 368
SP - 635
EP - 639
JO - Nature
JF - Nature
IS - 6472
ER -