Nitric oxide and long-term synaptic depression in the rat hippocampus

Neuroreport. 1993 Sep;4(9):1131-4.


Stimulation of the Schaffer collateral projection to the CA1 region in rat hippocampal slices at 1 Hz for 15 min produced a N-methyl-D-aspartate (NMDA) receptor-dependent long-term depression (LTD) of synaptic responses and, when given after tetanic stimulation, reversed long-term potentiation (LTP). Both LTD and the reversal of LTP were blocked by the nitric oxide (NO) inhibitor L-NG-monomethylargine (L-NMMA). L-NG-nitroarginine (L-NOArg) and hemoglobin also blocked LTD. The inhibition of LTD by L-NMMA was overcome by L- but not D-arginine. Sodium nitroprusside and S-nitrosocysteine, agents that spontaneously release NO, mimicked the effect of 1 Hz stimulation. These results indicate that NO mediates LTD produced by sustained 1 Hz activation of CA1 synapses and support the hypothesis that NO mediates the inhibition of LTP produced by untimely activation of NMDA receptors.

Publication types

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

MeSH terms

  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Carbon Monoxide / metabolism
  • Electric Stimulation
  • Hemoglobins / pharmacology
  • Hippocampus / cytology
  • Hippocampus / drug effects*
  • Hippocampus / physiology
  • In Vitro Techniques
  • Long-Term Potentiation / drug effects
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / physiology*
  • Nitroarginine
  • Nitroprusside / pharmacology
  • Rats
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Synapses / drug effects*
  • omega-N-Methylarginine


  • Hemoglobins
  • Receptors, N-Methyl-D-Aspartate
  • Nitroprusside
  • Nitroarginine
  • omega-N-Methylarginine
  • Nitric Oxide
  • Carbon Monoxide
  • Arginine