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Acute destruction of the synaptic ribbon reveals a role for the ribbon in vesicle priming

Nature Neuroscience volume 14, pages 1135–1141 (2011)Cite this article

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Abstract

In vision, balance and hearing, sensory receptor cells translate sensory stimuli into electrical signals whose amplitude is graded with stimulus intensity. The output synapses of these sensory neurons must provide fast signaling to follow rapidly changing stimuli while also transmitting graded information covering a wide range of stimulus intensity and must be able to sustain this signaling for long time periods. To meet these demands, specialized machinery for transmitter release, the synaptic ribbon, has evolved at the synaptic outputs of these neurons. We found that acute disruption of synaptic ribbons by photodamage to the ribbon markedly reduced both sustained and transient components of neurotransmitter release in mouse bipolar cells and salamander cones without affecting the ultrastructure of the ribbon or its ability to localize synaptic vesicles to the active zone. Our results indicate that ribbons mediate both slow and fast signaling at sensory synapses and support an additional role for the synaptic ribbon in priming vesicles for exocytosis at active zones.

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Figure 1: A synaptic ribbon-binding peptide exhibits irreversible photobleaching.
Figure 2: Ribbon-binding peptide has no effect on synaptic transmission.
Figure 3: Photodamage to the ribbon blocks replenishment of the immediately releasable pool in bipolar cell ribbon synapses.
Figure 4: Kinetic analysis of effects of photobleaching on AII postsynaptic response.
Figure 5: Effects of acute damage to cone photoreceptor ribbons on synaptic transmission.
Figure 6: Electron microscopy.

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Acknowledgements

The authors would like to thank S. Mentone for electron microscopy. This work was funded by US National Institutes of Health grants R01 EY003821 (G.M.), EY018111 (D.Z.) and EY10542 (W.T.), Yale University Vision Core grant EY000785 (M. Crair) and Research to Prevent Blindness (W.T.).

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Authors and Affiliations

  1. Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut, USA

    Josefin Snellman, Bhupesh Mehta, Adam Francis & David Zenisek

  2. Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska, USA

    Norbert Babai, Theodore M Bartoletti & Wallace Thoreson

  3. Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, New York, USA

    Wendy Akmentin & Gary Matthews

  4. Department of Ophthalmology and Visual Sciences, Yale University School of Medicine, New Haven, Connecticut, USA

    David Zenisek

  5. Center for Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, Connecticut, USA

    David Zenisek

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  1. Josefin Snellman
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Contributions

J.S. conducted the experiments shown in Figures 2, 3, 4 and 6, analyzed the data shown in Figures 2, 3 and 4 and contributed to the editing and writing of the manuscript. B.M. performed the experiments and analysis shown in Figure 3. N.B., T.M.B. and W.T. performed and analyzed the experiments shown in Figure 5. W.T. also contributed to the editing and writing of the manuscript. W.A. performed the electron microscopy shown in Figure 6 and the Supplementary Figures. A.F. performed experiments shown in Figure 1. G.M. oversaw the electron microscopy experiments and contributed to the editing and writing of the manuscript. D.Z. prepared the manuscript, oversaw the project, performed experiments shown in Figure 1 and performed the analysis shown in Figures 1 and 6.

Corresponding author

Correspondence to David Zenisek.

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Snellman, J., Mehta, B., Babai, N. et al. Acute destruction of the synaptic ribbon reveals a role for the ribbon in vesicle priming. Nat Neurosci 14, 1135–1141 (2011). https://doi.org/10.1038/nn.2870

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