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

Author

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  • Zachary F. Mainen

    (Cold Spring Harbor Laboratory)

  • Roberto Malinow

    (Cold Spring Harbor Laboratory)

  • Karel Svoboda

    (Cold Spring Harbor Laboratory)

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.

Suggested Citation

  • Zachary F. Mainen & Roberto Malinow & Karel Svoboda, 1999. "Synaptic calcium transients in single spines indicate that NMDA receptors are not saturated," Nature, Nature, vol. 399(6732), pages 151-155, May.
    • Handle: RePEc:nat:nature:v:399:y:1999:i:6732:d:10.1038_20187
    DOI: 10.1038/20187
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    Cited by:

    1. David M Santucci & Sridhar Raghavachari, 2008. "The Effects of NR2 Subunit-Dependent NMDA Receptor Kinetics on Synaptic Transmission and CaMKII Activation," PLOS Computational Biology, Public Library of Science, vol. 4(10), pages 1-16, October.
    2. Céline D. Dürst & J. Simon Wiegert & Christian Schulze & Nordine Helassa & Katalin Török & Thomas G. Oertner, 2022. "Vesicular release probability sets the strength of individual Schaffer collateral synapses," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Li, Tianyu & Wu, Yong & Yang, Lijian & Fu, Ziying & Jia, Ya, 2023. "Neuronal morphology and network properties modulate signal propagation in multi-layer feedforward network," Chaos, Solitons & Fractals, Elsevier, vol. 172(C).

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