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The diverse roles of ribbon synapses in sensory neurotransmission

Nature Reviews Neuroscience volume 11, pages 812–822 (2010)Cite this article

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Key Points

  • Ribbon synapses subserve transmitter release from 'tonic' sensory cells, including retinal photoreceptors and bipolar cells, and hair cells of vestibular, auditory and lateral line organs.

  • Synaptic 'ribbons' are electron-dense bodies attached to the plasma membrane at points of contact with postsynaptic neurons. Numerous small vesicles, likely to contain the neurotransmitter glutamate, are tethered to the ribbon. Ribbon structure, and presumably function, varies considerably among — and even within — different cell types.

  • Postsynaptic architecture of retinal photoreceptor ribbon synapses is complex, with glutamate released from a single ribbon reaching multiple functionally distinct targets. This divergence allows each point in visual space to be sampled in parallel by separate neural pathways concerned with different aspects of vision.

  • Vesicular fusion at ribbon synapses is driven by calcium influx through L-type, dihydropyridine-sensitive voltage-gated calcium channels. These have rapid activation and deactivation kinetics, and relatively little inactivation — consistent with the requirement to support ongoing, tonic release, and to vary rapidly with stimulus-evoked changes in membrane potential.

  • 'Tonic' vesicular release at ribbons differs qualitatively and quantitatively from 'phasic' release driven by action potentials at conventional neuronal synapses. Accordingly, ribbon synapses may employ a number of unique vesicle- and ribbon-associated proteins that differ from those of the canonical SNARE complex.

  • In addition to supporting impressive rates of ongoing vesicular release, ribbons seem also to employ a mechanism of 'multivesicular release' — simultaneous fusion of several synaptic vesicles that can occur without a coordinating change in membrane potential through as yet unknown means.

  • Ribbon synapses in hair cells of the mammalian cochlea meet special challenges; each one is the sole presynaptic source for an individual 'type I' cochlear afferent neuron, some of which have spontaneous activity of 100 action potentials per second, and stimulus-driven rates several times higher.

  • Remarkably, each cochlear inner hair cell is presynaptic to 10–30 afferent neurons, among which spontaneous rate, acoustic threshold and response dynamics differ. The emerging view is that individual ribbons of one hair cell can vary at least in the size of the ribbon and the number of associated voltage-gated calcium channels, although additional variations in synaptic release proteins and/or calcium metabolism could further contribute to functional variation.

  • Ribbon synapses seem to be capable of multiple modes of transmission, which could coexist to different degrees depending on the demands of a particular sensory system. Therefore, it seems that ribbon synapses are at least as diverse as conventional synapses. It remains to be determined how the presynaptic and postsynaptic architectures of the various ribbon-type synapses are adjusted to achieve this functional diversity.

Abstract

Sensory synapses of the visual and auditory systems must faithfully encode a wide dynamic range of graded signals, and must be capable of sustained transmitter release over long periods of time. Functionally and morphologically, these sensory synapses are unique: their active zones are specialized in several ways for sustained, rapid vesicle exocytosis, but their most striking feature is an organelle called the synaptic ribbon, which is a proteinaceous structure that extends into the cytoplasm at the active zone and tethers a large pool of releasable vesicles. But precisely how does the ribbon function to support tonic release at these synapses? Recent genetic and biophysical advances have begun to open the 'black box' of the synaptic ribbon with some surprising findings and promise to resolve its function in vision and hearing.

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Figure 1: Diversity of ribbon morphology and postsynaptic architecture in different cell types.
Figure 2: Modes of synaptic vesicle fusion at ribbon synapses.
Figure 3: Variable ribbon function within one cochlear inner hair cell.

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References

  1. Dick, O. et al. The presynaptic active zone protein bassoon is essential for photoreceptor ribbon synapse formation in the retina. Neuron 37, 775–786 (2003).

    Article  CAS  PubMed  Google Scholar 

  2. Heidelberger, R., Thoreson, W. B. & Witkovsky, P. Synaptic transmission at retinal ribbon synapses. Prog. Retin. Eye Res. 24, 682–720 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Sterling, P. & Matthews, G. Structure and function of ribbon synapses. Trends Neurosci. 28, 20–29 (2005).

    Article  CAS  PubMed  Google Scholar 

  4. DeVries, S. H., Li, W. & Saszik, S. Parallel processing in two transmitter microenvironments at the cone photoreceptor synapse. Neuron 50, 735–748 (2006).

    Article  CAS  PubMed  Google Scholar 

  5. von Gersdorff, H., Vardi, E., Matthews, G. & Sterling, P. Evidence that vesicles on the synaptic ribbon of retinal bipolar neurons can be rapidly released. Neuron 16, 1221–1227 (1996).

    Article  CAS  PubMed  Google Scholar 

  6. Jackman, S. L. et al. Role of the synaptic ribbon in transmitting the cone light response. Nature Neurosci. 12, 303–310 (2009). This study characterized release from cone photoreceptor ribbon synapses and suggested that ribbons operate in a partially depleted state, which serves to accentuate transient responses to dimming of illumination.

    Article  CAS  PubMed  Google Scholar 

  7. Calkins, D. J., Schein, S. J., Tsukamoto, Y. & Sterling, P. M and L cones in macaque fovea connect to midget ganglion cells by different numbers of excitatory synapses. Nature 371, 70–72 (1994).

    Article  CAS  PubMed  Google Scholar 

  8. Moser, T., Brandt, A. & Lysakowski, A. Hair cell ribbon synapses. Cell Tissue Res. 326, 347–359 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Brandt, A., Khimich, D. & Moser, T. Few Cav1.3 channels regulate the exocytosis of a synaptic vesicle at the hair cell ribbon synapse. J. Neurosci. 25, 11577–11585 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Meyer, A. C. et al. Tuning of synapse number, structure and function in the cochlea. Nature Neurosci. 12, 444–453 (2009). This study examined variations in ribbon number, size and intracellular distribution in inner hair cells along the cochlea's tonotopic axis. Fluorescent indicators revealed substantial variability in calcium 'hotspots', even within single inner hair cells.

    Article  CAS  PubMed  Google Scholar 

  11. Zampini, V. et al. Elementary properties of Cav1.3 Ca2+ channels expressed in mouse cochlear inner hair cells. J. Physiol. 588, 187–199 (2010). In this paper, single-channel recording from inner hair cells of the mouse cochlea provided additional estimates of the numbers of channels associated with each active zone (∼180 per ribbon) and the maximum open probability (∼0.15).

    Article  CAS  PubMed  Google Scholar 

  12. Pangrsic, T. et al. Hearing requires otoferlin-dependent efficient replenishment of synaptic vesicles in hair cells. Nature Neurosci. 13, 869–876 (2010).

    Article  CAS  PubMed  Google Scholar 

  13. Khimich, D. et al. Hair cell synaptic ribbons are essential for synchronous auditory signalling. Nature 434, 889–894 (2005).

    Article  CAS  PubMed  Google Scholar 

  14. Zenisek, D., Davila, V., Wan, L. & Almers, W. Imaging calcium entry sites and ribbon structures in two presynaptic cells. J. Neurosci. 23, 2538–2548 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Frank, T., Khimich, D., Neef, A. & Moser, T. Mechanisms contributing to synaptic Ca2+ signals and their heterogeneity in hair cells. Proc. Natl Acad. Sci. USA 106, 4483–4488 (2009). Fluorescent calcium indicators and calcium channel immunolabeling were used in this study to chart 'active zones' in cochlear inner hair cells. The covariation in the number of calcium channels and ribbon size found in this study may provide a mechanism for diversifying the activity of postsynaptic afferent neurons.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Nouvian, R., Beutner, D., Parsons, T. D. & Moser, T. Structure and function of the hair cell ribbon synapse. J. Membr. Biol. 209, 153–165 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Martinez-Dunst, C., Michaels, R. L. & Fuchs, P. A. Release sites and calcium channels in hair cells of the chick's cochlea. J. Neurosci. 17, 9133–9144 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. LoGiudice, L., Sterling, P. & Matthews, G. Mobility and turnover of vesicles at the synaptic ribbon. J. Neurosci. 28, 3150–3158 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Rea, R. et al. Streamlined synaptic vesicle cycle in cone photoreceptor terminals. Neuron 41, 755–766 (2004).

    Article  CAS  PubMed  Google Scholar 

  20. Holt, M., Cooke, A., Neef, A. & Lagnado, L. High mobility of vesicles supports continuous exocytosis at a ribbon synapse. Curr. Biol. 14, 173–183 (2004).

    Article  CAS  PubMed  Google Scholar 

  21. Zenisek, D. Vesicle association and exocytosis at ribbon and extraribbon sites in retinal bipolar cell presynaptic terminals. Proc. Natl Acad. Sci. USA 105, 4922–4927 (2008). Together with reference 18, this paper provided evidence for turnover of ribbon-associated synaptic vesicles during depolarization of retinal bipolar neurons.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Schaeffer, SF & Raviola, E. Membrane recycling in the cone cell endings of the turtle retina. J. Cell Biol. 79, 802–825 (1978).

    Article  CAS  PubMed  Google Scholar 

  23. Townes-Anderson, E., MacLeish, P. R. & Raviola, E. Rod cells dissociated from mature salamander retina, ultrastructure and uptake of horseradish peroxidase. J. Cell Biol. 100, 175–188 (1985).

    Article  CAS  PubMed  Google Scholar 

  24. Siegel, J. H. & Brownell, W. E. Synaptic and Golgi membrane recycling in cochlear hair cells. J. Neurocytol. 15, 311–328 (1986).

    Article  CAS  PubMed  Google Scholar 

  25. Paillart, C., Li, J., Matthews, G. & Sterling, P. Endocytosis and vesicle recycling at a ribbon synapse. J. Neurosci. 23, 4092–4099 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. LoGiudice, L., Sterling, P. & Matthews, G. Vesicle recycling at ribbon synapses in the finely branched axon terminals of mouse retinal bipolar neurons. Neuroscience 164, 1546–1556 (2009).

    Article  CAS  PubMed  Google Scholar 

  27. Matthews, G. & Sterling, P. Evidence that vesicles undergo compound fusion on the synaptic ribbon. J. Neurosci. 28, 5403–5411 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Lenzi, D., Crum, J., Ellisman, M. H. & Roberts, W. M. Depolarization redistributes synaptic membrane and creates a gradient of vesicles on the synaptic body at a ribbon synapse. Neuron 36, 649–659 (2002).

    Article  CAS  PubMed  Google Scholar 

  29. Zenisek, D., Horst, N. K., Merrifield, C., Sterling, P. & Matthews, G. Visualizing synaptic ribbons in the living cell. J. Neurosci. 24, 9752–9759 (2004). This study characterized a fluorescent peptide that binds to RIBEYE, the principal protein component of ribbons, and that allows ribbons to be localized in single synaptic terminals for live-cell imaging combined with electrophysiology.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Mennerick, S. & Matthews, G. Ultrafast exocytosis elicited by calcium current in synaptic terminals of retinal bipolar neurons. Neuron 17, 1241–1249 (1996).

    Article  CAS  PubMed  Google Scholar 

  31. von Gersdorff, H., Sakaba, T., Berglund, K. & Tachibana, M. Submillisecond kinetics of glutamate release from a sensory synapse. Neuron 21, 1177–1188 (1998).

    Article  CAS  PubMed  Google Scholar 

  32. Singer, J. H. & Diamond, J. S. Sustained Ca2+ entry elicits transient postsynaptic currents at a retinal ribbon synapse. J. Neurosci. 23, 10923–10933 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Thoreson, W. B., Rabl, K., Townes-Anderson, E. & Heidelberger, R. A highly Ca2+-sensitive pool of vesicles contributes to linearity at the rod photoreceptor ribbon synapse. Neuron 42, 595–605 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Bartoletti, T. M., Babai, N. & Thoreson, W. B. Vesicle pool size at the salamander cone ribbon synapse. J. Neurophysiol. 103, 419–423 (2010).

    Article  CAS  PubMed  Google Scholar 

  35. Midorikawa, M., Tsukamoto, Y., Berglund, K., Ishii, M. & Tachibana, M. Different roles of ribbon-associated and ribbonfree active zones in retinal bipolar cells. Nature Neurosci. 10, 1268–1276 (2007).

    Article  CAS  PubMed  Google Scholar 

  36. Coggins, M. R., Grabner, C. P., Almers, W. & Zenisek, D. Stimulated exocytosis of endosomes in goldfish retinal bipolar neurons. J. Physiol. 584, 853–865 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Palmer, M. J. Characterisation of bipolar cell synaptic transmission in goldfish retina using paired recordings. J. Physiol. 588, 1489–1498 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Hull, C., Studholme, K., Yazulla, S. & von Gersdorff, H. Diurnal changes in exocytosis and the number of synaptic ribbons at active zones of an ON-type bipolar cell terminal. J. Neurophysiol. 96, 2025–2033 (2006).

    Article  PubMed  Google Scholar 

  39. Snellman, J. & Zenisek, D. Photodamaging the ribbon disrupts coordination of multivesicular release and blocks vesicle replenishment at the rod bipolar cell synapse in mouse. Soc. Neurosci. Abstr. 522.7 (2009).

  40. Innocenti, B. & Heidelberger, R. Mechanisms contributing to tonic release at the cone photoreceptor ribbon synapse. J. Neurophysiol. 99, 25–36 (2008).

    Article  PubMed  Google Scholar 

  41. Moser, T. & Beutner, D. Kinetics of exocytosis and endocytosis at the cochlear inner hair cell afferent synapse of the mouse. Proc. Natl Acad. Sci. USA 97, 883–888 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Spassova, M. A. et al. Evidence that rapid vesicle replenishment of the synaptic ribbon mediates recovery from short-term adaptation at the hair cell afferent synapse. J. Assoc. Res. Otolaryngol. 5, 376–390 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Johnson, S. L., Marcotti, W. & Kros, C. J. Increase in efficiency and reduction in Ca2+ dependence of exocytosis during development of mouse inner hair cells. J. Physiol. 563, 177–191 (2005).

    Article  CAS  PubMed  Google Scholar 

  44. Edmonds, B. W., Gregory, F. D. & Schweizer, F. E. Evidence that fast exocytosis can be predominantly mediated by vesicles not docked at active zones in frog saccular hair cells. J. Physiol. 560, 439–450 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Singer, J. H., Lassova, L., Vardi, N. & Diamond, J. S. Coordinated multivesicular release at a mammalian ribbon synapse. Nature Neurosci. 7, 826–833 (2004).

    Article  CAS  PubMed  Google Scholar 

  46. Liberman, M. C. Single-neuron labeling in the cat auditory nerve. Science 216, 1239–1241 (1982).

    Article  CAS  PubMed  Google Scholar 

  47. Yi, E., Roux, I. & Glowatzki, E. Dendritic HCN channels shape excitatory postsynaptic potentials at the inner hair cell afferent synapse in the mammalian cochlea. J. Neurophysiol. 103, 2532–2543 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Liberman, M. C., Dodds, L. W. & Pierce, S. Afferent and efferent innervation of the cat cochlea, quantitative analysis with light and electron microscopy. J. Comp. Neurol. 301, 443–460 (1990).

    Article  CAS  PubMed  Google Scholar 

  49. Wu, Y. C., Tucker, T. & Fettiplace, R. A theoretical study of calcium microdomains in turtle hair cells. Biophys. J. 71, 2256–2275 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Zanazzi, G. & Matthews, G. The molecular architecture of ribbon presynaptic terminals. Mol. Neurobiol. 39, 130–148 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Platzer, J. et al. Congenital deafness and sinoartrial node dysfunction in mice lacking class D L-type Ca2+ channels. Cell 102, 89–97 (2000).

    Article  CAS  PubMed  Google Scholar 

  52. Nouvian, R. Temperature enhances exocytosis efficiency at the mouse inner hair cell ribbon synapse. J. Physiol. 584, 535–542 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Grant, L. & Fuchs, P. Calcium, calmodulin-dependent inactivation of calcium channels in inner hair cells of the rat cochlea. J. Neurophysiol. 99, 2183–2193 (2008).

    Article  PubMed  Google Scholar 

  54. Parsons, T. D., Lenzi, D., Almers, W. & Roberts, W. M. Calcium-triggered exocytosis and endocytosis in an isolated presynaptic cell, capacitance measurements in saccular hair cells. Neuron 13, 875–883 (1994).

    Article  CAS  PubMed  Google Scholar 

  55. Neef, A., Khimich, D., Pirih, P., Riedel, D., Wolf, F. & Moser, T. Probing the mechanism of exocytosis at the hair cell ribbon synapse. J. Neurosci. 27, 12933–12944 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Johnson, S. L., Forge, A., Knipper, M., Munkner, S. & Marcotti, W. Tonotopic variation in the calcium dependence of neurotransmitter release and vesicle pool replenishment at mammalian auditory ribbon synapses. J. Neurosci. 28, 7670–7678 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Beurg, M. et al. Calcium- and otoferlin-dependent exocytosis by immature outer hair cells. J. Neurosci. 28, 1798–1803 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Johnson, S. L., Franz, C., Knipper, M. & Marcotti, W. Functional maturation of the exocytotic machinery at gerbil hair cell ribbon synapses. J. Physiol. 587, 1715–1726 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Johnson, S. L. et al. Synaptotagmin IV determines the linear Ca2+ dependence of vesicle fusion at auditory ribbon synapses. Nature Neurosci. 13, 45–52 (2010).

    Article  CAS  PubMed  Google Scholar 

  60. Dulon, D., Safieddine, S., Jones, S. M. & Petit, C. Otoferlin is critical for a highly sensitive and linear calcium-dependent exocytosis at vestibular hair cell ribbon synapses. J. Neurosci. 29, 10474–10487 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Beutner, D. & Moser, T. The presynaptic function of mouse cochlear inner hair cells during development of hearing. J. Neurosci. 21, 4593–4599 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Furukawa, T., Hayashida, Y. & Matsuura, S. Quantal analysis of the size of excitatory post-synaptic potentials at synapses between hair cells and afferent nerve fibres in goldfish. J. Physiol. 276, 211–226 (1978).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Crawford, A. C. & Fettiplace, R. The frequency selectivity of auditory nerve fibres and hair cells in the cochlea of the turtle. J. Physiol. 306, 79–125 (1980).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Siegel, J. H. Spontaneous synaptic potentials from afferent terminals in the guinea pig cochlea. Hear. Res. 59, 85–92 (1992).

    Article  CAS  PubMed  Google Scholar 

  65. Glowatzki, E. & Fuchs, P. A. Transmitter release at the hair cell ribbon synapse. Nature Neurosci. 5, 147–154 (2002).

    Article  CAS  PubMed  Google Scholar 

  66. Keen, E. C. & Hudspeth, A. J. Transfer characteristics of the hair cell's afferent synapse. Proc. Natl Acad. Sci. USA 103, 5537–5542 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Li, G. L., Keen, E., Andor-Ardo, D., Hudspeth, A. J. & von Gersdorff, H. The unitary event underlying multiquantal EPSCs at a hair cell's ribbon synapse. J. Neurosci. 29, 7558–7568 (2009). In this study, paired presynaptic and postsynaptic recordings in the frog amphibian papilla were used to establish the response to a single vesicle. The larger postsynaptic responses that occurred with depolarization of the hair cell are presumed to be composed of multiple, simultaneously-released vesicles.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Maple, B. R., Werblin, F. S. & Wu, S. M. Miniature excitatory postsynaptic currents in bipolar cells of the tiger salamander retina. Vision Res. 34, 2357–2362 (1994).

    Article  CAS  PubMed  Google Scholar 

  69. Jarsky, T., Tian, M. & Singer, J. H. Nanodomain control of exocytosis is responsible for the signaling capability of a retinal ribbon synapse. J. Neurosci. 30, 11885–11895 (2010). In this study, paired recordings from bipolar cells and postsynaptic amacrine cells revealed small (single vesicle) release events when presynaptic calcium channel gating was rare. With presynaptic depolarization larger, multivesicular release events occurred.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Goutman, J. D. & Glowatzki, E. Time course and calcium dependence of transmitter release at a single ribbon synapse. Proc. Natl Acad. Sci. USA 104, 16341–16346 (2007). This study showed that paired recordings from inner hair cells and type I afferent dendrites describe a 'linear' synaptic transfer function. This is explained by an increase in release probability, with no change in the average amplitude of postsynaptic currents.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Grant, L., Yi, E. & Glowatzki, E. Two modes of release shape the postsynaptic response at the inner hair cell ribbon synapse. J. Neurosci. 30, 4210–4220 (2010). In this study, postsynaptic currents were recorded in dendrites of type I cochlear afferents from older rats (up to 2 months of age). As at younger synapses, postsynaptic currents were widely variable in size and the amplitude distribution was unchanged by hair cell depolarization. The fraction of smaller 'multiphasic' currents varied between synapses, but on average were fewer than in younger synapses.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Weisz, C., Glowatzki, E. & Fuchs, P. The postsynaptic function of type II cochlear afferents. Nature 461, 1126–1129 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Roberts, W. M. Localization of calcium signals by a mobile calcium buffer in frog saccular hair cells. J. Neurosci. 14, 3246–3262 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Rose, J. E., Brugge, J. F., Anderson, D. J. & Hind, J. E. Phase-locked response to low-frequency tones in single auditory nerve fibers of the squirrel monkey. J. Neurophysiol. 30, 769–793 (1967).

    Article  CAS  PubMed  Google Scholar 

  75. Griesinger, C. B., Richards, C. D. & Ashmore, J. F. Fast vesicle replenishment allows indefatigable signalling at the first auditory synapse. Nature 434, 212–215 (2005).

    Article  CAS  Google Scholar 

  76. Wittig, J. H. & Parsons, T. D. Synaptic ribbon enables temporal precision of hair cell afferent synapse by increasing the number of readily releasable vesicles: a modeling study. J. Neurophysiol. 100, 1724–1739 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  77. Buran, B. N. et al. Onset coding is degraded in auditory nerve fibers from mutant mice lacking synaptic ribbons. J. Neurosci. 30, 7587–7597 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Fuchs, P. A. Time and intensity coding at the hair cell's ribbon synapse. J. Physiol. 566, 7–12 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Brandstätter, J. H., Fletcher, E. L., Garner, C. C., Gundelfinger, E. D. & Wässle, H. Differential expression of the presynaptic cytomatrix protein bassoon among ribbon synapses in the mammalian retina. Eur. J. Neurosci. 11, 3683–3693 (1999).

    Article  PubMed  Google Scholar 

  80. tom Dieck, S. et al. Molecular dissection of the photoreceptor ribbon synapse, physical interaction of Bassoon and RIBEYE is essential for the assembly of the ribbon complex. J. Cell Biol. 168, 825–836 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Deguchi-Tawarada, M. et al. Active zone protein CAST is a component of conventional and ribbon synapses in mouse retina. J. Comp. Neurol. 495, 480–496 (2006).

    Article  CAS  PubMed  Google Scholar 

  82. Schmitz, F. A., Konigstorfer, A. & Südhof, T. C. RIBEYE, a component of synaptic ribbons, a protein's journey through evolution provides insight into synaptic ribbon function. Neuron 28, 857–872 (2000).

    Article  CAS  PubMed  Google Scholar 

  83. Magupalli, V. G. et al. Multiple RIBEYE–RIBEYE interactions create a dynamic scaffold for the formation of synaptic ribbons. J. Neurosci. 28, 7954–7967 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Usukura, J. & Yamada, E. Ultrastructure of the synaptic ribbons in photoreceptor cells of Rana catesbeiana revealed by freeze-etching and freeze-substitution. Cell Tissue Res. 247, 483–488 (1987).

    Article  CAS  PubMed  Google Scholar 

  85. Wang, Y., Okamoto, M., Schmitz, F., Hofmann, K. & Südhof, T. C. Rim is a putative Rab3 effector in regulating synaptic-vesicle fusion. Nature 388, 593–598 (1997).

    Article  CAS  PubMed  Google Scholar 

  86. Muresan, V., Lyass, A. & Schnapp, B. J. The kinesin motor KIF3A is a component of the presynaptic ribbon in vertebrate photoreceptors. J. Neurosci. 19, 1027–1037 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Dick, O., Hack, I., Altrock, W. D., Garner, C. C., Gundelfinger, E. D. & Brandstätter, J. H. Localization of the presynaptic cytomatrix protein Piccolo at ribbon and conventional synapses in the rat retina, comparison with Bassoon. J. Comp. Neurol. 439, 224–234 (2001).

    Article  CAS  PubMed  Google Scholar 

  88. Venkatesan, J. K. et al. Nicotinamide adenine dinucleotide-dependent binding of the neuronal Ca2+ sensor protein GCAP2 to photoreceptor synaptic ribbons. J. Neurosci. 30, 6559–6576 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Curtis, L. B. et al. Syntaxin 3b is a t-SNARE specific for ribbon synapses of the retina. J. Comp. Neurol. 510, 550–559 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Curtis, L. et al. Syntaxin 3B is essential for the exocytosis of synaptic vesicles in ribbon synapses of the retina. Neuroscience 166, 832–841 (2010).

    Article  CAS  PubMed  Google Scholar 

  91. Reim, K. et al. Structurally and functionally unique complexins at retinal ribbon synapses. J. Cell Biol. 169, 669–680 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Roux, I. et al. Otoferlin, defective in a human deafness form, is essential for exocytosis at the auditory ribbon synapse. Cell 127, 277–289 (2006).

    Article  CAS  PubMed  Google Scholar 

  93. Duncan, G., Rabl, K., Gemp, I., Heidelberger, R. & Thoreson, W. B. Quantitative analysis of synaptic release at the photoreceptor synapse. Biophys. J. 98, 2102–2110 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Beutner, D., Voets, T., Neher, E. & Moser, T. Calcium dependence of exocytosis and endocytosis at the cochlear inner hair cell afferent synapse. Neuron 29, 681–690 (2001).

    Article  CAS  PubMed  Google Scholar 

  95. von Gersdorff, H. & Matthews, G. Calcium-dependent inactivation of calcium current in synaptic terminals of retinal bipolar neurons. J. Neurosci. 16, 115–122 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Zidanic, M. & Fuchs, P. A. Kinetic analysis of barium currents in chick cochlear hair cells. Biophys. J. 68, 1323–1336 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Mennerick, S. & Matthews, G. Rapid calcium-current kinetics in synaptic terminals of goldfish retinal bipolar neurons. Vis. Neurosci. 15, 1051–1056 (1998).

    Article  CAS  PubMed  Google Scholar 

  98. Tachibana, M., Okada, T., Arimura, T., Kobayashi, K. & Piccolino, M. Dihydropyridine-sensitive calcium current mediates neurotransmitter release from bipolar cells of the goldfish retina. J. Neurosci. 13, 2898–2909 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Heidelberger, R. & Matthews, G. Calcium influx and calcium current in single synaptic terminals of goldfish retinal bipolar neurons. J. Physiol. 447, 235–256 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Schmitz, Y. & Witkovsky, P. Glutamate release by the intact light-responsive photoreceptor layer of the Xenopus retina. J. Neurosci. Methods 68, 55–60 (1996).

    Article  CAS  PubMed  Google Scholar 

  101. Robertson, D. & Paki, B. Role of L-type Ca2+ channels in transmitter release from mammalian inner hair cells. II. Single-neuron activity. J. Neurophysiol. 87, 2734–2740 (2002).

    Article  CAS  PubMed  Google Scholar 

  102. Zhang, S. Y., Robertson, D., Yates, G. & Everett, A. Role of L-type Ca2+ channels in transmitter release from mammalian inner hair cells, I. Gross sound-evoked potentials. J. Neurophysiol. 82, 3307–3315 (1999).

    Article  CAS  PubMed  Google Scholar 

  103. Bech-Hansen, N. T. et al. Loss-of-function mutations in a calcium-channel α1-subunit gene in Xp11.23 cause incomplete X-linked congenital stationary night blindness. Nature Genet. 19, 264–267 (1998).

    Article  CAS  PubMed  Google Scholar 

  104. Strom, T. M. et al. An L-type calcium-channel gene mutated in incomplete X-linked congenital stationary night blindness. Nature Genet. 19, 260–263 (1998).

    Article  CAS  PubMed  Google Scholar 

  105. Mansergh, F. et al. Mutation of the calcium channel gene Cacna1f disrupts calcium signaling, synaptic transmission and cellular organization in mouse retina. Hum. Mol. Genet. 14, 3035–3046 (2005).

    Article  CAS  PubMed  Google Scholar 

  106. Morgans, C. W. Localization of the α1F calcium channel subunit in the rat retina. Invest. Ophthalmol. Vis. Sci. 42, 2414–2418 (2001).

    CAS  PubMed  Google Scholar 

  107. Wässle, H., Haverkamp, S., Grünert, U. & Morgans, C. W. in The Neural Basis of Early Vision. (ed. Kaneko, A.) 19–38 (Springer Verlag, Tokyo, 2003).

    Google Scholar 

  108. Haeseleer, F. et al. Essential role of Ca2+-binding protein 4, a Cav1.4 channel regulator, in photoreceptor synaptic function. Nature Neurosci. 7, 1079–1087 (2004).

    Article  CAS  PubMed  Google Scholar 

  109. Zeitz, C. et al. Mutations in CABP4, the gene encoding the Ca2+-binding protein 4, cause autosomal recessive night blindness. Am. J. Hum. Genet. 79, 657–667 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Kollmar, R., Montgomery, L. G., Fak, J., Henry, L. J. & Hudspeth, A. J. Predominance of the α1D subunit in L-type voltage-gated Ca2+ channels of hair cells in the chicken's cochlea. Proc. Natl Acad. Sci. USA 94, 14883–14888 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Michna, M. et al. Cav1.3 (α1D) Ca2+ currents in neonatal outer hair cells of mice. J. Physiol. 553, 747–758 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Brandt, A., Striessnig, J. & Moser, T. Cav1.3 channels are essential for development and presynaptic activity of cochlear inner hair cells. J. Neurosci. 23, 10832–10840 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Harlow, M. L., Ress, D., Stoschek, A., Marshall, R. M. & McMahan, U. J. The architecture of active zone material at the frog's neuromuscular junction. Nature 409, 479–484 (2001).

    Article  CAS  PubMed  Google Scholar 

  114. Zampighi, G. A. et al. Conical electron tomography of a chemical synapse, polyhedral cages dock vesicles to the active zone. J. Neurosci. 28, 4151–4160 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Siksou, L. et al. Three-dimensional architecture of presynaptic terminal cytomatrix. J. Neurosci. 27, 6868–6877 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Zhai, R. G. & Bellen, H. J. The architecture of the active zone in the presynaptic nerve terminal. Physiology 19, 262–270 (2004).

    Article  PubMed  Google Scholar 

  117. Rao-Mirotznik, R., Harkins, A. B., Buchsbaum, G. & Sterling, P. Mammalian rod terminal, architecture of a binary synapse. Neuron 14, 561–569 (1995).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors are supported by the National Institutes of Health (National Eye Institute grant R01EY003821 to G.M.) and the National Institute on Deafness and other Communication Disorders (grants R01DC000276, R01DC001508 and P30 DC005211 to P.F.)

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Authors and Affiliations

  1. Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, 11794-5230, New York, USA

    Gary Matthews

  2. The Center for Hearing and Balance, Otolaryngology, Head and Neck Surgery and the Center for Sensory Biology, Johns Hopkins University School of Medicine, Ross 818, 720 Rutland Avenue, Baltimore, 21205, Maryland, USA

    Paul Fuchs

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Glossary

Freeze-fracture

A technique for 'three-dimensional' imaging of cellular ultrastructure by coating the surface of fractured tissue with electron-dense material.

SNARE

Soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein (SNAP) receptor.

ON bipolar cell

Bipolar cells are classed as either ON or OFF depending on how they respond to glutamate released in their vicinity by photoreceptors. ON bipolar cells respond to a lowering of released glutamate by depolarizing, and OFF bipolar cells respond to this change by becoming hyperpolarized.

Tonotopic

The mapping of tones of different frequencies onto space along a receptive surface, such as the mammalian cochlea, or onto different spatial locations within a brain nucleus that processes auditory information.

Capacitance

Electrical measure of charge-storing capacity. Cell membranes behave as electrical capacitors because the insulating lipid separates two electrically conductive salt solutions. The capacitance of a cell is proportional to the cell's surface area and thus serves as an index of membrane addition and retrieval.

Cytomatrix at the active zone

The complex of membrane-associated and cytoplasmic proteins that provide structural organization for the many components required to dock, prime and fuse synaptic vesicles at presynaptic active zones.

Pleiomorphic

Varied in shape.

Voltage-clamp

A fundamental electrophysiological technique for measuring ionic currents in cells while 'clamping' the membrane potential to prevent changes caused by those currents.

'Mini'

Shorthand for miniature postsynaptic current, which is the current produced by spontaneous or evoked exocytosis of a single synaptic vesicle.

Cable loss

The decrement of 'passive' voltage signals along neuronal processes.

Phase-locking

Precise timing between two signals. In the auditory system, phase-locking refers to coordination between action potentials in auditory neurons, and the cycles of a tonal stimulus.

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Matthews, G., Fuchs, P. The diverse roles of ribbon synapses in sensory neurotransmission. Nat Rev Neurosci 11, 812–822 (2010). https://doi.org/10.1038/nrn2924

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