Long-term potentiation in the hippocampal CA1 region of mice lacking cGMP-dependent kinases is normal and susceptible to inhibition of nitric oxide synthase

Thomas Kleppisch, Alexander Pfeifer, Peter Klatt, Peter Ruth, Alexandra Montkowski, Reinhard Fässler, Franz Hofmann

Research output: Contribution to journalArticlepeer-review

106 Scopus citations

Abstract

Long-term potentiation (LTP) is a potential cellular mechanism for learning and memory. The retrograde messenger nitric oxide (NO) is thought to induce LTP in the CA1 region of the hippocampus via activation of soluble guanylyl cyclase (sGC) and, ultimately, cGMP-dependent protein kinase (cGK). Two genes code for the isozymes cGKI and cGKII in vertebrates. The functional role of cGKs in LTP was analyzed using mice lacking the gene(s) for cGKI, cGKII, or both. LTP was not altered in the mutant mice lineages. However, LTP was reduced by inhibition of NO synthase and NMDA receptor antagonists, respectively. The reduced LTP was not recovered by the cGK-activator 8-(4 chlorophenylthio)-cGMP. Moreover, LTP was not affected by the sGC inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]-quiloxalin-1-one. In contrast, it was effectively suppressed by nicotinamide, a blocker of the ADP-ribosyltransferase. These results show that cGKs are not involved in LTP in mice and that NO induces LTP through an alternative cGMP-independent pathway, possibly ADP- ribosylation.

Original languageEnglish
Pages (from-to)48-55
Number of pages8
JournalJournal of Neuroscience
Volume19
Issue number1
DOIs
StatePublished - 1 Jan 1999

Keywords

  • Gene targeting
  • Hippocampus
  • Mouse
  • Nitric oxide
  • Synaptic plasticity
  • cGMP-dependent kinase

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