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Synaptic calcium transients in single spines indicate that NMDA receptors are not saturated

Nature volume 399, pages 151–155 (1999)Cite this article

Abstract

At excitatory synapses in the central nervous system, the number of glutamate molecules released from a vesicle is much larger than the number of postsynaptic receptors. But does release of a single vesicle normally saturate these receptors? Answering this question is critical to understanding how the amplitude and variability of synaptic transmission are set and regulated. Here we describe the use of two-photon microscopy1 to image transient increases in Ca2+ concentration mediated by NMDA (N -methyl-D-aspartate) receptors in single dendritic spines of CA1 pyramidal neurons in hippocampal slices. To test for NMDA-receptor saturation, we compared responses to stimulation with single and double pulses. We find that a single release event does not saturate spine NMDA receptors; a second release occurring 10 ms later produces ∼80% more NMDA-receptor activation. The amplitude of spine NMDA-receptor-mediated [Ca2+] transients (and the synaptic plasticity which depends on this) may thus be sensitive to the number of quanta released by a burst of action potentials and to changes in the concentration profile of glutamate in the synaptic cleft.

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Figure 1: Probabilistic activation of NMDA receptors monitored by imaging spine [Ca2+] transients.
Figure 2: Time course of NMDA-R currents and spine fluorescence transients.
Figure 3: NMDA receptors are not saturated following a single action potential.
Figure 4: Quantification of NMDA-R response linearity (see Methods for calculation).

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Acknowledgements

This work was supported by a Burroughs Wellcome Career Award (Z.F.M.), grants from NIH and the Mather's Foundation (R.M.), and grants from the Pew and Whitaker Foundations (K.S.).

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  1. Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, 11724, New York, USA

    Zachary F. Mainen, Roberto Malinow & Karel Svoboda

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  1. Zachary F. Mainen
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  3. Karel Svoboda
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Correspondence to Karel Svoboda.

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Mainen, Z., Malinow, R. & Svoboda, K. Synaptic calcium transients in single spines indicate that NMDA receptors are not saturated. Nature 399, 151–155 (1999). https://doi.org/10.1038/20187

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