Regulation by glycine, Mg2+ and polyamines of the N-methyl-d-aspartate-induced locomotion in the neonatal rat spinal cord in vitro
Section snippets
Dissection
Experiments were performed on 34 Wistar rats aged one to four days. The animals were deeply anesthetized with ether before decapitation. A laminectomy was done to expose the spinal cord and to remove it. The spinal cord, cut at the thoracic level, was then placed in a recording chamber. The preparation was superfused (3 ml/min) with an oxygenated (95% O2/5% CO2) saline (composition in mM: NaCl 130; KCl 3; CaCl2 3.75; MgSO4 1.3; NaH2PO4 0.58; NaHCO3 25; glucose 10). The solution was adjusted to
Effects of 7-chlorokynurenic acid on the locomotor synaptic inputs on motoneurons
The superfusion of NMA/5-HT or of NMA alone on the lumbar spinal cord (Fig. 2A1) initiated locomotor-like activity which was recorded extracellularly from the L2 ventral roots and intracellularly from a motoneuron (Fig. 2A2). This stereotypical locomotor pattern consisted of bursts of action potentials alternating between the right and left side of each lumbar segment and between the ipsilateral L2 and L5 ventral roots.7., 20., 26.
In order to test whether glycine regulates the excitatory part
Discussion
The results of the present study show that the various allosteric mechanisms controlling the NMDA receptor are already at work at birth. First, the NMDA part of the excitatory synaptic inputs conveyed by the L1–L2 network to the motoneurons is under the control of endogenous glycine. Secondly, the NMA-induced locomotion is positively controlled by glycine and negatively controlled by both Mg2+ and spermine in the neonatal rat spinal cord.
Most of the studies done on the regulation of the NMDA
Conclusion
This study shows that, at birth, the complex allosteric regulatory mechanisms are already at work regulating NMDA receptor activity. As for glycine, it appears to act at multiple levels of locomotor processes. As NMDA receptors are transiently overexpressed in the developing spinal cord,18 glycine, Mg2+ and spermine may play an important role in developmental regulation by determining the level of activity of the NMDA currents in the neonatal rat.
Acknowledgements
The authors wish to thank Dr H. Burnet for his help in statistical analysis, G. Riviere for her technical assistance and Dr F. Clarac and K. Duff for reading and correcting the manuscript. Many thanks to R. Navarro for nursing the pups.
References (42)
- et al.
Effects of magnesium on fictive locomotion induced by activation of N-methyl-d-aspartate (NMDA) receptors in the lamprey spinal cord in vitro
Brain Res.
(1986) - et al.
Strychnine eliminates alternating motor output during fictive locomotion in the lamprey
Brain Res.
(1984) - et al.
The neural network underlying locomotion in lamprey—synaptic and cellular mechanisms
Neuron
(1991) - et al.
Voltage dependent block by intracellular Mg2+ of N-methyl-d-aspartate-activated channels
Biophy. J.
(1990) - et al.
N-Methyl-d,l-aspartate induced locomotor activity in a spinal cord-hindlimb muscles preparation of the newborn rat studied in vitro
Neurosci. Lett.
(1987) - et al.
Selective depression of the spinal polysynaptic reflex by the NMDA receptor antagonists in an isolated spinal cord in vitro
Gen. Pharmac.
(1997) - et al.
NMDA receptor activation by spermine requires glutamate but not glycine
Eur. J. Pharmac. molec. Pharmac.
(1993) Arcaine is a competitive antagonist of the polyamine site on the NMDA receptor
Eur. J. Pharmac.
(1990)- et al.
A cooling/heating system for use with in vitro preparation: study of temperature effects on newborn rat activities
J. Neurosci. Meth.
(1991) - et al.
Characterization of polyamines having agonist, antagonist, and inverse agonist effects at the polyamine recognition site of the NMDA receptor
Neuron
(1990)
Multiple effects of spermine on N-methyl-d-aspartate acid responses of rat cultured hippocampal neurones
J. Physiol., Lond.
Postinhibitory rebound during locomotor-like activity in neonatal rat motoneurons in vitro
J. Neurophysiol.
Spontaneous rhythmic bursts induced by pharmacological block of inhibition in lumbar motoneurons of the neonatal rat spinal cord
J. Neurophysiol.
Localization and organization of the central pattern generator for hindlimb locomotion in newborn rat
J. Neurosci.
The synaptic drive from the spinal locomotor network to motoneurons in the newborn rat
J. Neurosci.
Activation of the central pattern generators for locomotion by serotonin and excitatory amino acids in neonatal rat
J. Physiol., Lond.
Regional distribution of the locomotor pattern-generating network in the neonatal rat spinal cord
J. Neurophysiol.
Effects of inhibitory amino acid antagonists on reciprocal inhibitory interactions during rhythmic motor activity in the in vitro neonatal rat spinal cord
J. Neurophysiol.
Reciprocal inhibitory interneurones in the Xenopus embryo spinal cord
J. Physiol.
7-Chlorokynurenic acid blocks the NMDA receptor-induced locomotion in lamprey—evidence for a physiological role of the glycine site
Acta physiol. scand.
Cited by (7)
Glycine plays a crucial role as a co-agonist of NMDA receptors in the neuronal circuit generating body movements in rat fetuses
2015, Neuroscience ResearchCitation Excerpt :In the neonatal rat spinal cord in vitro, activation of the NMDA receptor induces locomotor-like rhythmic motor activities in both neonatal and fetal in vitro preparations (Kudo and Yamada, 1987; Ozaki et al., 1996). It has also been shown that 7-chlorokynurenic acid, an antagonist of the glycine binding site of the NMDA receptor, increases the decreased locomotor rhythmic activity and decreased burst amplitude (Bertrand and Cazalets, 1999). The importance of the glycine binding site of the NMDA receptor for the generation of locomotion seems to be shared across species.
An anti-immobility effect of spermine in the forced swim test in mice
2014, Pharmacological ReportsCitation Excerpt :No stereotyped behaviour was observed either. Moreover, Bertrand and Cazalets [3] reported that spermine antagonised the inhibitory action of arcaine on locomotion. Therefore, it could be suspected that the decrease in the immobility after the spermine treatment was not encouraged by any motor effect.
Do pacemakers drive the central pattern generator for locomotion in mammals?
2010, NeuroscientistIs NMDA receptor activation essential for the production of locomotor-like activity in the neonatal rat spinal cord?
2005, Journal of Neurophysiology