The role of nitric oxide in hippocampal long-term potentiation

Neuron. 1992 Feb;8(2):211-6. doi: 10.1016/0896-6273(92)90288-o.


Long-term potentiation is a long-lasting, use-dependent increase in the strength of synaptic connections. We investigated the role of nitric oxide (NO) in determining the duration of potentiation induced by high frequency stimulation of afferents in the CA1 region of the rat hippocampus. The calcium/calmodulin-dependent production of NO can be initiated by activation of excitatory amino acid receptors and results in increased levels of cGMP in target cells. Here we report that only a relatively short-term potentiation can be induced in the presence of nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor. The effects of L-NAME on the duration of potentiation are partially reversed by coadministration of L-arginine, a precursor of neuronal NO, and by dibutyryl cGMP. Hemoglobin, which binds extracellular NO, also shortens the duration of stimulus-induced potentiation. The results suggest a role for NO in the maintenance of activity-dependent synaptic enhancements, possibly via the generation of cGMP.

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
  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Calcium / physiology
  • Calmodulin / physiology
  • Cyclic GMP / metabolism
  • Dibutyryl Cyclic GMP / pharmacology
  • Hemoglobins / pharmacology
  • Hippocampus / metabolism
  • Hippocampus / physiology*
  • Male
  • NG-Nitroarginine Methyl Ester
  • Neuronal Plasticity / physiology
  • Nitric Oxide / pharmacology*
  • Nitric Oxide Synthase
  • Rats
  • Synapses / physiology
  • Time Factors


  • Calmodulin
  • Hemoglobins
  • Nitric Oxide
  • Dibutyryl Cyclic GMP
  • Arginine
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases
  • Cyclic GMP
  • Calcium
  • NG-Nitroarginine Methyl Ester