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  Developmental refinement of hair cell synapses tightens the coupling of Ca2+ influx to exocytosis

Wong, A. B., Rutherford, M. A., Gabrielaitis, M., Pangrsic, T., Göttfert, F., Frank, T., et al. (2014). Developmental refinement of hair cell synapses tightens the coupling of Ca2+ influx to exocytosis. The EMBO Journal, 33(3), 247-264. doi:10.1002/embj.201387110.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0029-0F73-1 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0029-0F74-0
Genre: Journal Article

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 Creators:
Wong, Aaron B., Author
Rutherford, Mark A., Author
Gabrielaitis, Mantas1, Author              
Pangrsic, Tina, Author
Göttfert, Fabian, Author
Frank, Thomas, Author
Michanski, Susann, Author
Hell, Stefan, Author
Wolf, Fred1, 2, Author              
Wichmann, Carolin, Author
Moser, Tobias, Author
Affiliations:
1Research Group Theoretical Neurophysics, Max Planck Institute for Dynamics and Self-Organization, Max Planck Society, ou_2063289              
2Department of Nonlinear Dynamics, Max Planck Institute for Dynamics and Self-Organization, Max Planck Society, ou_2063286              

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 Abstract: Cochlear inner hair cells (IHCs) develop from pre‐sensory pacemaker to sound transducer. Here, we report that this involves changes in structure and function of the ribbon synapses between IHCs and spiral ganglion neurons (SGNs) around hearing onset in mice. As synapses matured they changed from holding several small presynaptic active zones (AZs) and apposed postsynaptic densities (PSDs) to one large AZ/PSD complex per SGN bouton. After the onset of hearing (i) IHCs had fewer and larger ribbons; (ii) CaV1.3 channels formed stripe‐like clusters rather than the smaller and round clusters at immature AZs; (iii) extrasynaptic CaV1.3‐channels were selectively reduced, (iv) the intrinsic Ca2+ dependence of fast exocytosis probed by Ca2+ uncaging remained unchanged but (v) the apparent Ca2+ dependence of exocytosis linearized, when assessed by progressive dihydropyridine block of Ca2+ influx. Biophysical modeling of exocytosis at mature and immature AZ topographies suggests that Ca2+ influx through an individual channel dominates the [Ca2+] driving exocytosis at each mature release site. We conclude that IHC synapses undergo major developmental refinements, resulting in tighter spatial coupling between Ca2+ influx and exocytosis.

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Language(s): eng - English
 Dates: 2014-01-17
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: eDoc: 698881
DOI: 10.1002/embj.201387110
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Title: The EMBO Journal
Source Genre: Journal
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Pages: - Volume / Issue: 33 (3) Sequence Number: - Start / End Page: 247 - 264 Identifier: -