Inhibition of excitatory synaptic transmission in the trigeminal motor nucleus by the nitric oxide-cyclic GMP signaling pathway

Brain Res. 2011 Jun 1:1393:1-16. doi: 10.1016/j.brainres.2011.03.002. Epub 2011 Mar 8.


Nitric oxide (NO) and cyclic GMP (cGMP) suppressed glutamatergic synaptic transmission to trigeminal motoneurons in brain stem slices of neonatal rats. Histological studies showed guanylate cyclase (GC) containing fibers in the trigeminal motor pool. Glutamatergic excitatory postsynaptic currents (EPSCs) were recorded from neonatal trigeminal motoneurons in response to stimulation of the supratrigeminal nucleus (SuV). The NO donors DETA/NONOate (DETA/NO), at a concentration which released 275.1 nM of NO, and Spermine/NONOate (Sper/NO) reduced the amplitude of the EPSC to 52.7±0.6% and 60.1±10.8% of control values, respectively. These actions were not blocked by the GC inhibitors, ODQ or NS-2028. However, in the presence of YC-1 or BAY41-2272, modulators of GC that act as NO sensitizers, lower and otherwise ineffective concentrations of DETA/NO induced a reduction of the EPSC to 60.6±5.2%. Moreover, NO effects were mimicked by 8BrcGMP and by Zaprinast, an inhibitor of Phosphodiesterase 5. Glutamatergic currents evoked by exogenous glutamate were not reduced by DETA/NO nor 8BrcGMP. Paired-pulse facilitation was increased by NO donors. Under "minimal stimulation" conditions NO donors and cGMP increased the failure rate of evoked EPSCs. Protein kinase inhibitors antagonized cGMP effects. The results suggest that NO, through the synthesis of cGMP, presynaptically inhibits glutamatergic synaptic transmission on trigeminal motoneurons. We propose that NO has complex actions on motor pools; specific studies are needed to elucidate their physiological significance in the behaving animal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Cyclic GMP / analogs & derivatives
  • Cyclic GMP / metabolism*
  • Cyclic GMP / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology*
  • Glutamic Acid / physiology
  • Motor Neurons / drug effects
  • Motor Neurons / physiology*
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Nitric Oxide / metabolism*
  • Nitric Oxide Donors / pharmacology
  • Organ Culture Techniques
  • Presynaptic Terminals / physiology
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Triazenes / pharmacology
  • Trigeminal Nuclei / cytology
  • Trigeminal Nuclei / physiology*


  • 1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene
  • Nitric Oxide Donors
  • Triazenes
  • 8-bromocyclic GMP
  • Nitric Oxide
  • Glutamic Acid
  • Cyclic GMP