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Calcium-channel number critically influences synaptic strength and plasticity at the active zone

Nature Neuroscience volume 15, pages 998–1006 (2012)Cite this article

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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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Figure 1: Cell-attached patch recording of calcium currents at the calyx release face.
Figure 2: Active-zone density at the calyx release face matches patch electrophysiology.
Figure 3: Single calcium-channel conductance and probability of a channel being open ('open probability') at the release face.
Figure 4: The impact of the calcium-channel number on release strength.
Figure 5: Impact of calcium-channel number on the release probability and the number of RRVs.
Figure 6: The impact of Nchannel on paired-pulse plasticity and the open channel number during an action potential.
Figure 7: The open calcium-channel number during an action potential.

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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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Authors and Affiliations

  1. National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA

    Jiansong Sheng, Liming He, Lei Xue, Fujun Luo, Wonchul Shin, Tao Sun & Ling-Gang Wu

  2. Pharmacology Institute, Interdisciplinary Center for Scientific Computing, Heidelberg University, Heidelberg, Germany

    Hongwei Zheng

  3. Institute of Anatomy and Cell Biology, Heidelberg University, Heidelberg, Germany

    Hongwei Zheng & Thomas Kuner

  4. Departments of Biomedical Engineering and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    David T Yue

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Contributions

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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Correspondence to Ling-Gang Wu.

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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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