Developmental regulation of NMDA receptor-mediated synaptic currents at a central synapse

THE central nervous system has extraordinary plasticity in early life. This is thought to involve N-methyl-D-aspartate (NMDA) receptors1 which, along with the non-NMDA receptors, mediate fast excitatory synaptic transmission2. Although NMDA receptors may be transiently enhanced early in life3–6, it has not been possible to demonstrate directly a functional change in the NMDA receptor-mediated synaptic response because of the voltage-dependence of the NMDA conductance and the overlapping inhibitory synaptic conductances. Here I report that the duration of evoked NMDA-receptor-mediated excitatory postsynaptic currents (e.p.s.cs) in the superior colliculus is several times longer at early developmental stages compared to that measured in older animals. In contrast, the amplitude of NMDA-receptor-mediated miniature e.p.s.cs does not change during development. The kinetic response of excised membrane patches to a brief activation of NMDA receptors is similar to that of the NMDA e.p.s.c, which suggests that the time course of the NMDA e.p.s.c. in the superior colliculus reflects slow NMDA channel properties as in the hippocampus7–9. Therefore, these data indicate that the molecular properties of NMDA receptors are developmentally regulated and thus may be controlling the ability of synapses to change in early life.

[1]  J. Lund,et al.  Development of synaptic patterns in the superior colliculus of the rat. , 1972, Brain research.

[2]  M. Constantine-Paton,et al.  Patterned activity, synaptic convergence, and the NMDA receptor in developing visual pathways. , 1990, Annual review of neuroscience.

[3]  Y. Ben-Ari,et al.  Changes in voltage dependence of NMDA currents during development , 1988, Neuroscience Letters.

[4]  R. Nicoll,et al.  Analysis of excitatory synaptic action in pyramidal cells using whole‐cell recording from rat hippocampal slices. , 1990, The Journal of physiology.

[5]  Arnold R. Kriegstein,et al.  Whole cell recording from neurons in slices of reptilian and mammalian cerebral cortex , 1989, Journal of Neuroscience Methods.

[6]  Bert Sakmann,et al.  Molecular distinction between fetal and adult forms of muscle acetylcholine receptor , 1986, Nature.

[7]  R. Nicoll,et al.  Mechanisms generating the time course of dual component excitatory synaptic currents recorded in hippocampal slices , 1990, Neuron.

[8]  W Singer,et al.  The development of N-methyl-D-aspartate receptors in cat visual cortex. , 1989, Brain research. Developmental brain research.

[9]  W. Singer,et al.  Developmental changes in the susceptibility to long-term potentiation of neurones in rat visual cortex slices. , 1991, Brain research. Developmental brain research.

[10]  S. Nakanishi,et al.  Molecular cloning and characterization of the rat NMDA receptor , 1991, Nature.

[11]  L. Trussell,et al.  Glutamate receptor desensitization and its role in synaptic transmission , 1989, Neuron.

[12]  A. Kriegstein,et al.  Initial expression and endogenous activation of NMDA channels in early neocortical development , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[13]  S. Schuetze,et al.  A post‐natal decrease in acetylcholine channel open time at rat end‐plates. , 1980, The Journal of physiology.

[14]  L. Nowak,et al.  Magnesium gates glutamate-activated channels in mouse central neurones , 1984, Nature.

[15]  M. Mayer,et al.  Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones , 1984, Nature.

[16]  G. Westbrook,et al.  Channel kinetics determine the time course of NMDA receptor-mediated synaptic currents , 1990, Nature.

[17]  D. Colquhoun,et al.  Glutamate activation of a single NMDA receptorchannel produces a cluster of channel openings , 1991, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[18]  T. Tsumoto,et al.  NMDA receptors in the visual cortex of young kittens are more effective than those of adult cats , 1987, Nature.

[19]  R. Miller,et al.  Measurement of passive membrane parameters with whole-cell recording from neurons in the intact amphibian retina. , 1989, Journal of neurophysiology.

[20]  Y. Okada,et al.  Masking effect of NMDA receptor antagonists on the formation of long-term potentiation (LTP) in superior colliculus slices from the guinea pig , 1990, Brain Research.

[21]  B. Sakmann,et al.  Change in synaptic channel gating during neuromuscular development , 1978, Nature.

[22]  K. Fox,et al.  Dark-rearing delays the loss of NMDA-receptor function in kitten visual cortex , 1991, Nature.