Johnson, S.L., Wedemeyer, C., Vetter, D.E. et al. (4 more authors) (2013) Cholinergic efferent synaptic transmission regulates the maturation of auditory hair cell ribbon synapses. Open Biology, 3 (11). 130163. ISSN 2046-2441
Abstract
Spontaneous electrical activity generated by developing sensory cells and neurons is crucial for the maturation of neural circuits. The full maturation of mammalian auditory inner hair cells (IHCs) depends on patterns of spontaneous action potentials during a 'critical period' of development. The intrinsic spiking activity of IHCs can be modulated by inhibitory input from cholinergic efferent fibres descending from the brainstem, which transiently innervate immature IHCs. However, it remains unknown whether this transient efferent input to developing IHCs is required for their functional maturation. We used a mouse model that lacks the α9-nicotinic acetylcholine receptor subunit (α9nAChR) in IHCs and another lacking synaptotagmin-2 in the efferent terminals to remove or reduce efferent input to IHCs, respectively. We found that the efferent system is required for the developmental linearization of the Ca(2+)-sensitivity of vesicle fusion at IHC ribbon synapses, without affecting their general cell development. This provides the first direct evidence that the efferent system, by modulating IHC electrical activity, is required for the maturation of the IHC synaptic machinery. The central control of sensory cell development is unique among sensory systems.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | & 2013 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0/, which permits unrestricted use, provided the original author and source are credited. |
Keywords: | Action Potentials; Animals; Cochlea; Hair Cells, Auditory, Inner; Mice; Mice, Knockout; Motor Neurons; Receptors, Nicotinic; Stereocilia; Synapses; Synaptic Transmission; Synaptotagmin II |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 20 Dec 2016 13:50 |
Last Modified: | 20 Dec 2016 13:50 |
Published Version: | http://dx.doi.org/10.1098/rsob.130163 |
Status: | Published |
Publisher: | The Royal Society |
Refereed: | Yes |
Identification Number: | 10.1098/rsob.130163 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:108275 |