Noncholinergic excitatory actions of motoneurons in the neonatal mammalian spinal cord

doi:10.1073/pnas.0502788102

Noncholinergic excitatory actions of motoneurons in the neonatal mammalian spinal cord

^*Laboratory of Neural Control, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892; and ^‡Department of Anatomy and Physiology, Wright State University, Dayton, OH 45435

Communicated by Lynn T. Landmesser, Case Western Reserve University, Cleveland, OH, April 7, 2005 (received for review February 11, 2005)

Abstract

Mammalian spinal motoneurons are considered to be output elements of the spinal cord that generate exclusively cholinergic actions on Renshaw cells, their intraspinal synaptic targets. Here, we show that antidromic stimulation of motor axons evokes depolarizing monosynaptic potentials in Renshaw cells that are depressed, but not abolished, by cholinergic antagonists. This residual potential was abolished by 2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione. In the presence of cholinergic antagonists, motor axon stimulation triggered locomotor-like activity that was blocked by 2-amino-5-phosphonovaleric acid. Some cholinergic motoneuronal terminals on both Renshaw cells and motoneurons were enriched in glutamate, but none expressed vesicular glutamate transporters. Our results raise the possibility that motoneurons release an excitatory amino acid in addition to acetylcholine and that they may be more directly involved in the genesis of mammalian locomotion than previously believed.

Footnotes

↵ † To whom correspondence should be addressed. E-mail: mentisg{at}ninds.nih.gov.
Author contributions: G.Z.M., F.J.A., and M.J.O. designed research; G.Z.M., F.J.A., A.B., D.S.R., D.G.-F. and R.Z. performed research; G.Z.M., F.J.A., A.B., D.S.R., D.G.-F. and M.J.O. analyzed data; and M.J.O. wrote the paper.
Abbreviations: EAA, excitatory amino acid neurotransmitter; VAChT, vesicular acetylcholine transporter; IR, immunoreactive; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; APV, 2-amino-5-phosphonovaleric acid; CNQX, 6-cyano-7-nitroquinoxaline-2,3-dione; VGLUT, vesicular glutamate transporter.
↵ § Mentis, G. Z., Alvarez, F. J., Geiman, E. J. & O'Donovan, M. J. (2003) Soc. Neurosci. Abstr. (abstr.).
Freely available online through the PNAS open access option.