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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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.
The authors declare no competing financial interests.
[Ca2+] relaxation model (PDF 238 kb)
Correlation between EPSC amplitude and the peak and half-width of ΔF/F transients. (PDF 340 kb)
Ca2+ sensor model. (PDF 237 kb)
Kinetic rate constants used in the [Ca2+] relaxation model. (PDF 103 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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