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Role of the synaptic ribbon in transmitting the cone light response

Nature Neuroscience volume 12, pages 303–310 (2009)Cite this article

Abstract

Cone photoreceptors distinguish small changes in light intensity while operating over a wide dynamic range. The cone synapse encodes intensity by modulating tonic neurotransmitter release, but precise encoding is limited by the quantal nature of synaptic vesicle exocytosis. Cones possess synaptic ribbons, structures that are thought to accelerate the delivery of vesicles for tonic release. Here we show that the synaptic ribbon actually constrains vesicle delivery, resulting in a maintained state of synaptic depression in darkness. Electron microscopy of cones from the lizard Anolis segrei revealed that depression is caused by the depletion of vesicles on the ribbon, indicating that resupply, not fusion, is the rate-limiting step that controls release. Responses from postsynaptic retinal neurons from the salamander Ambystoma tigrinum showed that the ribbon behaves like a capacitor, charging with vesicles in light and discharging in a phasic burst at light offset. Phasic release extends the operating range of the cone synapse to more accurately encode changes in light intensity, accentuating features that are salient to photopic vision.

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Figure 1: Light stimulation collapses a Ca2+ gradient that is maintained in cone terminals in darkness.
Figure 2: Elevation of cone terminal Ca2+ reveals two kinetic components of release.
Figure 3: Ca2+ dependence of phasic and tonic release.
Figure 4: Electron microscopy of ribbon-associated vesicles.
Figure 5: Phasic release of resupplied vesicles on ribbons underlies the off response of postsynaptic neurons.
Figure 6: The kinetics of vesicle resupply on the ribbon.
Figure 7: Phasic release improves the encoding of a change in luminance.

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Acknowledgements

We thank D. Fortin, R. Heidelberger and F. Werblin for comments on the manuscript, R.S. Zucker for advice on Ca2+ imaging and R. Zalpuri for help with electron microscopy. This work was supported by grants from Research to Prevent Blindness to W.B.T. and the US National Institutes of Health to R.H.K. (EY015514) and W.B.T. (EY10542).

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Author notes

  1. Sue-Yeon Choi & Katalin Rabl

    Present address: Present address: Department of Ophthalmology, University of California San Francisco, San Francisco, California 94143, USA.,

  2. Skyler L Jackman, Sue-Yeon Choi and Wallace B Thoreson: These authors contributed equally to this work.

Authors and Affiliations

  1. Departments of Physics, University of California Berkeley, Berkeley, 94720, California, USA

    Skyler L Jackman

  2. Molecular and Cell Biology, University of California Berkeley, Berkeley, 94720, California, USA

    Sue-Yeon Choi & Richard H Kramer

  3. Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, 68198, Nebraska, USA

    Wallace B Thoreson, Katalin Rabl & Theodore M Bartoletti

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Contributions

S.L.J., S.-Y.C., W.B.T. and R.H.K. conceived the experiments; S.L.J. and S.-Y.C. performed the imaging experiments and analyzed the data; K.R., T.M.B. and W.B.T. carried out the electrophysiology experiments; S.L.J. performed data analysis and modeling; and S.L.J. and R.H.K. co-wrote the paper.

Corresponding author

Correspondence to Richard H Kramer.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–6, Supplementary Tables 1 and 2, and Supplementary Methods (PDF 751 kb)

Supplementary Movie 1 (GIF format)

A video illustration showing how depletion and resupply affect synaptic transmission of the cone light response. Vesicles bind to the ribbon, descend towards the base and fuse with the plasma membrane near open Ca2+ channels. (GIF 1019 kb)

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Jackman, S., Choi, SY., Thoreson, W. et al. Role of the synaptic ribbon in transmitting the cone light response. Nat Neurosci 12, 303–310 (2009). https://doi.org/10.1038/nn.2267

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