Concentration dynamics of nitric oxide in rat hippocampal subregions evoked by stimulation of the NMDA glutamate receptor

Proc Natl Acad Sci U S A. 2005 Nov 29;102(48):17483-8. doi: 10.1073/pnas.0503624102. Epub 2005 Nov 17.


Nitric oxide (*NO) production in response to stimulation of the NMDA glutamate receptor is implicated not only in the synaptic plasticity in hippocampus but may also participate in excitotoxic cell death. Using *NO-selective microssensors inserted into the diffusional field of *NO in acute hippocampal slices, we describe the *NO concentration dynamics evoked by NMDA receptor activation and report profound differences along the trisynaptic loop of the hippocampus. We measured the oxygen gradient across the slice thickness and conclude that *NO measurements were performed at cell layers experiencing physiological oxygen tensions. Recordings performed at increasing distances from the point of NMDA receptor stimulation resulted in a progressive decrease of *NO signals, reaching undetectable levels for distances >400 microm, supporting the notion of a wide diffusional spread of endogenously generated *NO in the hippocampus. Neither a picoinjection nor a continuous perfusion of NMDA resulted in high steady-state *NO levels; rather all signals were transient, suggesting that cells are able to efficiently respond to high *NO concentrations (typically 200-400 nM) bringing it to very low nM levels; the claimed high micromolar *NO range achieved by excessive stimulation of NMDA receptor may have to be reevaluated. The distinct responses to NMDA receptor stimulation along the trysynaptic loop suggest a differential *NO activity and/or regulation among the hippocampal subregions. These findings may be relevant for the understanding of the role of *NO in physiologic mechanisms in the hippocampus and the differential sensitivity of the hippocampal subregions to NMDA receptor-dependent neurodegeneration.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diffusion
  • Electrophysiology
  • Hippocampus / metabolism
  • Hippocampus / physiology*
  • Histological Techniques
  • Male
  • Nitric Oxide / metabolism*
  • Oxygen / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / metabolism*


  • Receptors, N-Methyl-D-Aspartate
  • Nitric Oxide
  • Oxygen