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

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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Figure 1: Transient [Ca2+] elevations evoked by photolysis of DM-nitrophen in the presence of Ca2+ buffers.
Figure 2: Dependence of glutamate release on the time course of the [Ca2+] transient.
Figure 3: Predictions of a kinetic model of the Ca2+ sensor.
Figure 4: Mimicking AP-evoked release with fast [Ca2+] transients.
Figure 5: Release triggered by paired [Ca2+] transients.
Figure 6: Simulated impact of [Ca2+] profile on EPSC amplitudes.
Figure 7: Comparison of different Ca2+ sensor models.

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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.

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Correspondence to Johann H Bollmann.

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Supplementary information

Supplementary Fig. 1

[Ca2+] relaxation model (PDF 238 kb)

Supplementary Fig. 2

Correlation between EPSC amplitude and the peak and half-width of ΔF/F transients. (PDF 340 kb)

Supplementary Fig. 3

Ca2+ sensor model. (PDF 237 kb)

Supplementary Table 1

Kinetic rate constants used in the [Ca2+] relaxation model. (PDF 103 kb)

Supplementary Methods (PDF 92 kb)

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Bollmann, J., Sakmann, B. Control of synaptic strength and timing by the release-site Ca2+ signal. Nat Neurosci 8, 426–434 (2005). https://doi.org/10.1038/nn1417

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