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Role of guanylyl cyclase and cGMP-dependent protein kinase in long-term potentiation

Nature volume 368, pages 635–639 (1994)Cite this article

Abstract

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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Authors and Affiliations

  1. Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University,

    Min Zhuo, Yinghe Hu, Eric R. Kandel & Robert D. Hawkins

  2. New York State Psychiatric Institute,

    Eric R. Kandel & Robert D. Hawkins

  3. Howard Hughes Medical Institute, 722 West 168th Street, New York, New York, 10032, USA

    Min Zhuo & Eric R. Kandel

  4. Department of Pharmacology, University of California, San Diego, California, 92093, USA

    Carsten Schultz

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  1. Min Zhuo
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  2. Yinghe Hu
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  4. Eric R. Kandel
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  5. Robert D. Hawkins
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Zhuo, M., Hu, Y., Schultz, C. et al. Role of guanylyl cyclase and cGMP-dependent protein kinase in long-term potentiation. Nature 368, 635–639 (1994). https://doi.org/10.1038/368635a0

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