Abstract
How synaptic-vesicle release is controlled at the basic release structure, the active zone, is poorly understood. By performing cell-attached current and capacitance recordings predominantly at single active zones in rat calyces, we found that single active zones contained 5−218 (mean, 42) calcium channels and 1−10 (mean, 5) readily releasable vesicles (RRVs) and released 0−5 vesicles during a 2-ms depolarization. Large variation in the number of calcium channels caused wide variation in release strength (measured during a 2-ms depolarization) by regulating the RRV release probability (PRRV) and the RRV number. Consequently, an action potential opened ∼1–35 (mean, ∼7) channels, resulting in different release probabilities at different active zones. As the number of calcium-channels determined PRRV, it critically influenced whether subsequent release would be facilitated or depressed. Regulating calcium channel density at active zones may thus be a major mechanism to yield synapses with different release properties and plasticity. These findings may explain large differences reported at synapses regarding release strength (release of 0, 1 or multiple vesicles), PRRV, short-term plasticity, calcium transients and the requisite calcium-channel number for triggering release.
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Acknowledgements
We thank K. Sätzler and J. Lübke for providing the electron microscopy data for analysis, and J. Diamond, J. Xu and M. Baydyuk for comments on the manuscript. This work was supported by the US National Institute of Neurological Disorders and Stroke Intramural Research Program.
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J.S. performed most experiments, designed experiments and participated in writing the paper. L.H. designed experiments and developed the method of patching single active zones. L.X. recorded whole-cell calcium currents in the presence of the P/Q-type channel blocker. F.L. participated in designing experiments. H.Z. and T.K. performed computational analysis of the active-zone density. D.T.Y. ensured low-noise single-channel recordings and contributed to experimental design. W.S. and T.S. assisted the project. L.-G.W. designed experiments, supervised the project and wrote the paper.
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Sheng, J., He, L., Zheng, H. et al. Calcium-channel number critically influences synaptic strength and plasticity at the active zone. Nat Neurosci 15, 998–1006 (2012). https://doi.org/10.1038/nn.3129
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DOI: https://doi.org/10.1038/nn.3129
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