Endothelial NOS and the blockade of LTP by NOS inhibitors in mice lacking neuronal NOS

Science. 1994 Jul 22;265(5171):542-6. doi: 10.1126/science.7518615.


Long-term potentiation (LTP) is a persistent increase in synaptic strength implicated in certain forms of learning and memory. In the CA1 region of the hippocampus, LTP is thought to involve the release of one or more retrograde messengers from the postsynaptic cell that act on the presynaptic terminal to enhance transmitter release. One candidate retrograde messenger is the membrane-permeant gas nitric oxide (NO), which in the brain is released after activation of the neuronal-specific NO synthase isoform (nNOS). To assess the importance of NO in hippocampal synaptic plasticity, LTP was examined in mice where the gene encoding nNOS was disrupted by gene targeting. In nNOS- mice, LTP induced by weak intensity tetanic stimulation was normal except for a slight reduction in comparison to that in wild-type mice and was blocked by NOS inhibitors, just as it was in wild-type mice. Immunocytochemical studies indicate that in the nNOS- mice as in wild-type mice, the endothelial form of NOS (eNOS) is expressed in CA1 neurons. These findings suggest that eNOS, rather than nNOS, generates NO within the postsynaptic cell during LTP.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Oxidoreductases / antagonists & inhibitors
  • Amino Acid Oxidoreductases / genetics
  • Amino Acid Oxidoreductases / metabolism*
  • Animals
  • Arginine / analogs & derivatives*
  • Arginine / pharmacology
  • Electric Stimulation
  • Endothelium / enzymology
  • Hippocampus / drug effects
  • Hippocampus / enzymology
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Long-Term Potentiation* / drug effects
  • Mice
  • Mutation
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase
  • Nitroarginine
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / enzymology
  • Pyramidal Cells / physiology*
  • Synaptic Transmission / drug effects


  • Nitroarginine
  • Nitric Oxide
  • Arginine
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases