The Journal of Neurophysiology Vol. 80 No. 1 July 1998, pp. 196-208
Copyright ©1998 The American Physiological Society

Endogenous NMDA-Receptor Activation Regulates Glutamate Release in Cultured Spinal Neurons

Antoine Robert, Joel A. Black, and Stephen G. Waxman

Department of Neurology, Yale University School of Medicine, New Haven 06510; and PVA/EPVA Neuroscience Research Center, Veterans Affairs Medical Center, West Haven, Connecticut 06516

Robert, Antoine, Joel A. Black, and Stephen G. Waxman. Endogenous NMDA-receptor activation regulates glutamate release in cultured spinal neurons. J. Neurophysiol. 80: 196-208, 1998. N-methyl-D-aspartate (NMDA) receptor activation plays a fundamental role in the genesis of electrical activity of immature neurons and may participate in activity-dependent aspects of CNS development. A recent study has suggested that NMDA-receptor-mediated glutamatergic neurotransmission might occur in the developing spinal cord via activation of nonsynaptic receptors, but the details of NMDA-receptor activation in the developing CNS are not yet well understood. We describe here a model of cultured spinal neurons that display ongoing -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor activity characterized by spontaneous excitatory postsynaptic currents (EPSCs), with NMDA-receptor activity detectable only as single channel events. DL-2-amino-5-phosphonovaleric acid (100 µM) and tetrodotoxin (TTX) 100 nM each reduced the occurrence of spontaneous AMPA EPSCs; quantal analysis showed a decrease in the number of released quanta but no changes in quantal size, indicating that NMDA-receptor activation and Na⁺ channel activity affect the generation of spontaneous AMPA EPSCs, at least in part, via mechanisms that impinge on the presynaptic terminal. Once the Mg²⁺-block was released, activity of NMDA receptors dramatically increased the release of quantal and multiquantal amounts of glutamate, indicating that the NMDA receptors are physiologically coupled to glutamate release. In Mg²⁺-free solution, TTX application elicited an increase in the number of quantal AMPA EPSCs and a reduction in the number of multiquantal EPSCs, consistent with an effect of NMDA-receptor activation on presynaptic terminals. Our results suggest that endogenous activity at a small number of NMDA receptors can regulate the release of neurotransmitters at developing AMPA synapses.

This article has been cited by other articles:

				G. Woodhall, D. I. Evans, M. O. Cunningham, and R. S. G. Jones NR2B-Containing NMDA Autoreceptors at Synapses on Entorhinal Cortical Neurons J Neurophysiol, October 1, 2001; 86(4): 1644 - 1651. [Abstract] [Full Text] [PDF]

				V. L. Arvanov, B. S. Seebach, and L. M. Mendell NT-3 Evokes an LTP-Like Facilitation of AMPA/Kainate Receptor-Mediated Synaptic Transmission in the Neonatal Rat Spinal Cord J Neurophysiol, August 1, 2000; 84(2): 752 - 758. [Abstract] [Full Text] [PDF]

				A. Robert, J. R. Howe, and S. G. Waxman Development of Glutamatergic Synaptic Activity in Cultured Spinal Neurons J Neurophysiol, February 1, 2000; 83(2): 659 - 670. [Abstract] [Full Text] [PDF]

				D. W. Ali, R. R. Buss, and P. Drapeau Properties of Miniature Glutamatergic EPSCs in Neurons of the Locomotor Regions of the Developing Zebrafish J Neurophysiol, January 1, 2000; 83(1): 181 - 191. [Abstract] [Full Text] [PDF]

				A. J. Cochilla and S. Alford NMDA Receptor-Mediated Control of Presynaptic Calcium and Neurotransmitter Release J. Neurosci., January 1, 1999; 19(1): 193 - 205. [Abstract] [Full Text] [PDF]