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Excitatory synapses

Neither too loud nor too quiet

Nature volume 399, pages 111–112 (1999)Cite this article

A striking feature of many excitatory synapses in the central nervous system is that the neurotransmitter glutamate simultaneously activates receptors with very different pharmacological properties. Notably, AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors open and close rapidly and mediate fast signalling, whereas NMDA (N -methyl-d-aspartate) receptors have slow, voltage-dependent kinetics, are permeable to calcium, and are central to the induction of long-term synaptic plasticity. On page 151of this issue, a report by Mainen et al.1 challenges a widespread assumption about how glutamate activates NMDA receptors.

For AMPA and NMDA receptors to detect the release of glutamate from presynaptic terminals, the concentration of this neurotransmitter in the synaptic cleft must be enough to activate them. Accurate estimates of the glutamate concentration after exocytosis have been obtained by measuring the sensitivity of AMPA or NMDA-mediated synaptic signals to rapidly dissociating antagonists — the higher the concentration of glutamate, the more easily the antagonist is displaced from the receptors2. These (and other) experimental approaches have converged on a picture where AMPA receptors are activated by the release of a single vesicle, although the receptors may not be saturated3,4,5. But NMDA receptors are predicted to be almost completely occupied, the difference being explained by their 100-fold higher affinity for glutamate6. This conclusion agrees with the results of experiments that simulated diffusion of a few thousand glutamate molecules in the sticky and tortuous environment of the synaptic cleft7.

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Figure 1: Occupancy of AMPA and NMDA receptors after release of the neurotransmitter glutamate.

References

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Authors and Affiliations

  1. Department of Clinical Neurology, Institute of Neurology, Queen Square, University College London, London, WC1N 3BG, UK

    Dimitri M. Kullmann

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  1. Dimitri M. Kullmann
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Kullmann, D. Neither too loud nor too quiet. Nature 399, 111–112 (1999). https://doi.org/10.1038/20089

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