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Hair cell synaptic ribbons are essential for synchronous auditory signalling


Hearing relies on faithful synaptic transmission at the ribbon synapse of cochlear inner hair cells (IHCs)1,2,3. At present, the function of presynaptic ribbons at these synapses is still largely unknown1,4. Here we show that anchoring of IHC ribbons is impaired in mouse mutants for the presynaptic scaffolding protein Bassoon. The lack of active-zone-anchored synaptic ribbons reduced the presynaptic readily releasable vesicle pool, and impaired synchronous auditory signalling as revealed by recordings of exocytic IHC capacitance changes and sound-evoked activation of spiral ganglion neurons. Both exocytosis of the hair cell releasable vesicle pool and the number of synchronously activated spiral ganglion neurons co-varied with the number of anchored ribbons during development. Interestingly, ribbon-deficient IHCs were still capable of sustained exocytosis with normal Ca2+-dependence. Endocytic membrane retrieval was intact, but an accumulation of tubular and cisternal membrane profiles was observed in ribbon-deficient IHCs. We conclude that ribbon-dependent synchronous release of multiple vesicles at the hair cell afferent synapse is essential for normal hearing.

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Figure 1: Bassoon anchors synaptic ribbons at IHC active zones.
Figure 2: Synaptic ribbons are essential for hearing and fast exocytosis from hair cells.
Figure 3: Fast exocytosis and compound action potential amplitude correlate with the number of anchored ribbons per IHCs during development.
Figure 4: Dissection of ribbon-dependent hair cell exocytosis.

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  1. Fuchs, P. A., Glowatzki, E. & Moser, T. The afferent synapse of cochlear hair cells. Curr. Opin. Neurobiol. 13, 452–458 (2003)

    Article  CAS  Google Scholar 

  2. Smith, C. A. & Sjostrand, F. S. A synaptic structure in the hair cells of the guinea pig cochlea. J. Ultrastruct. Res. 5, 184–192 (1961)

    Article  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  5. Lagnado, L. Ribbon synapses. Curr. Biol. 13, R631 (2003)

    Article  CAS  Google Scholar 

  6. Schmitz, F., Konigstorfer, A. & Sudhof, 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  Google Scholar 

  7. Dick, O. et al. 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  Google Scholar 

  8. 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. (in the press); published online 22 February 2005 (doi:10.1083/jcb.200408157)

  9. tom Dieck, S. et al. Bassoon, a novel zinc-finger CAG/glutamine-repeat protein selectively localized at the active zone of presynaptic nerve terminals. J. Cell Biol. 142, 499–509 (1998)

    Article  CAS  Google Scholar 

  10. 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  Google Scholar 

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

    Article  CAS  Google Scholar 

  12. 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  Google Scholar 

  13. Holt, M., Cooke, A., Wu, M. M. & Lagnado, L. Bulk membrane retrieval in the synaptic terminal of retinal bipolar cells. J. Neurosci. 23, 1329–1339 (2003)

    Article  CAS  Google Scholar 

  14. Hell, S. & Stelzer, E. H. K. Properties of a 4Pi-confocal fluorescence microscope. J. Opt. Soc. Am. A 18, 2159–2166 (1992)

    Article  ADS  Google Scholar 

  15. Egner, A., Jakobs, S. & Hell, S. W. Fast 100-nm resolution three-dimensional microscope reveals structural plasticity of mitochondria in live yeast. Proc. Natl Acad. Sci. USA 99, 3370–3375 (2002)

    Article  ADS  CAS  Google Scholar 

  16. Kemp, D. T. Stimulated acoustic emissions from within the human auditory system. J. Acoust. Soc. Am. 64, 1386–1391 (1978)

    Article  ADS  CAS  Google Scholar 

  17. Starr, A., Picton, T. W., Sininger, Y., Hood, L. J. & Berlin, C. I. Auditory neuropathy. Brain 119, 741–753 (1996)

    Article  Google Scholar 

  18. 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  ADS  CAS  Google Scholar 

  19. Shnerson, A., Devigne, C. & Pujol, R. Age-related changes in the C57BL/6J mouse cochlea. II. Ultrastructural findings. Brain Res. 254, 77–88 (1981)

    Article  CAS  Google Scholar 

  20. Neher, E. Vesicle pools and Ca2+ microdomains: new tools for understanding their roles in neurotransmitter release. Neuron 20, 389–399 (1998)

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  22. Trussell, L. O. Synaptic mechanisms for coding timing in auditory neurons. Annu. Rev. Physiol. 61, 477–496 (1999)

    Article  CAS  Google Scholar 

  23. Heidelberger, R., Heinemann, C., Neher, E. & Matthews, G. Calcium dependence of the rate of exocytosis in a synaptic terminal. Nature 371, 513–515 (1994)

    Article  ADS  CAS  Google Scholar 

  24. Zenisek, D., Steyer, J. A. & Almers, W. Transport, capture and exocytosis of single synaptic vesicles at active zones. Nature 406, 849–854 (2000)

    Article  ADS  CAS  Google Scholar 

  25. 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. (Lond.) 560, 439–450 (2004)

    Article  CAS  Google Scholar 

  26. 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  Google Scholar 

  27. 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  Google Scholar 

  28. Smith, J. E. & Reese, T. S. Use of aldehyde fixatives to determine the rate of synaptic transmitter release. J. Exp. Biol. 89, 19–29 (1980)

    CAS  PubMed  Google Scholar 

  29. 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  Google Scholar 

  30. Altrock, W. D. et al. Functional inactivation of a fraction of excitatory synapses in mice deficient for the active zone protein bassoon. Neuron 37, 787–800 (2003)

    Article  CAS  Google Scholar 

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We would like to thank A. Brandt and A. Schoenle for providing custom analysis software; S. Anderson and S. Lacas-Gervais for help in setting up auditory physiology and immunohistochemistry in the InnerEarLab, respectively; and J. H. Brandstaetter, F. Wolf and S. W. Hell for discussions and suggestions; members of the InnerEarLab for counting of spots and discussion; E. Neher, T. Sakaba, L. Lagnado, C. Kubisch, M. C. Liberman and E. Livesey for comments on the manuscript; F. Kirchhoff and M. Lenoir for help with confocal and electron microscopy, respectively; and M. Köppler, F. Tribillac and C. Cazevieille for technical assistance. We would like to thank M. Eybalin for initial collaboration. This work was supported by grants from the Deutsche Forschungsgemeinschaft to T.M. and to E.D.G., by a Tandem-Project of the Max Planck Society (to E. Neher and T.M.), a Human Frontiers in Science Program grant to T.M., a grant from the Fonds der Chemischen Industrie to E.D.G, and a grant from Acouphènes-Languedoc-Roussillon to J.-L. Puel.

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Correspondence to Tobias Moser.

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Supplementary information

Supplementary Figure S1

This file contains images that support the morphological results of this study. (DOC 518 kb)

Supplementary Figure S2

This file presents recordings of sound-evoked cochlear potentials and otoacoustic emissions. (DOC 370 kb)

Supplementary Figure S3

This file details the hair cell physiology of the mice used in the study. (DOC 803 kb)

Supplementary Table S1

This details the quantification of our light and electron microscopy of WT and mutant synapses and relates morphological findings to physiology. (DOC 54 kb)

Supplementary Movie S1a

This movie displays an animated 3D-reconstruction of a WT organ of Corti to illustrate the quantitative confocal synapse analysis. We counted 68 GluR spots (red) and 64 ribbon-containing synapses (juxtaposed red GluR and green RIBEYE spots) in 6 IHCs (green nuclei). (MPG 561 kb)

Supplementary Movie S1b

This movie displays an animated 3D-reconstruction of a mutant organ of Corti, where we counted 53 GluR spots and 12 ribbon-containing synapses in 7 IHCs. (MPG 561 kb)

Supplementary Methods

This file describes additional methods used in this study, including the 4Pi microscopy and model of size distribution. (DOC 23 kb)

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

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