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Control of synaptic strength and timing by the release-site Ca2+ signal

Nature Neuroscience volume 8, pages 426434 (2005) | Download Citation

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  • An Erratum to this article was published on 01 July 2005

Abstract

Transmitter release is triggered by highly localized, transient increases in the presynaptic Ca2+ concentration ([Ca2+]). Rapidly decaying [Ca2+] elevations were generated using Ca2+ uncaging techniques, and [Ca2+] was measured with a low-affinity Ca2+ indicator in a giant presynaptic terminal, the calyx of Held, in rat brain slices. The rise time and amplitude of evoked excitatory postsynaptic currents (EPSCs) depended on the half-width of the fluorescence transient, which was predicted by a five–binding site model of a Ca2+ sensor having relatively high affinity (Kd 13 μM). Very fast [Ca2+] transients (half-width <0.5 ms) evoked EPSCs similar to those elicited by a single action potential (AP) in the same synapse. Triggering release with dual [Ca2+] transients of variable amplitudes demonstrated the supralinear transfer function of the sensor. The sensitivity of release to the time course of the [Ca2+] transient may contribute to mechanisms by which the presynaptic AP waveform controls synaptic strength.

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Acknowledgements

We thank J.G.G. Borst, R.M. Bruno, E. Neher and R.S. Zucker for helpful discussions and comments on an earlier version of the manuscript, and M. Kaiser, R. Rödel and K. Schmidt for expert technical assistance. We consistently used a calibrated lot (#3491) of OGB-5N, of which a part was kindly provided by T. Euler and K. Svoboda.

Author information

Author notes

    • Johann H Bollmann

    Present address: Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA.

Affiliations

  1. Abteilung Zellphysiologie, Max-Planck-Institut für medizinische Forschung, Jahnstrasse 29, D-69120 Heidelberg, Germany.

    • Johann H Bollmann
    •  & Bert Sakmann

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Johann H Bollmann.

Supplementary information

PDF files

  1. 1.

    Supplementary Fig. 1

    [Ca2+] relaxation model

  2. 2.

    Supplementary Fig. 2

    Correlation between EPSC amplitude and the peak and half-width of ΔF/F transients.

  3. 3.

    Supplementary Fig. 3

    Ca2+ sensor model.

  4. 4.

    Supplementary Table 1

    Kinetic rate constants used in the [Ca2+] relaxation model.

  5. 5.

    Supplementary Methods

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DOI

https://doi.org/10.1038/nn1417