Cholinergic efferent synaptic transmission regulates the maturation of auditory hair cell ribbon synapses. Issue 11 (November 2013)

• Record Type: Journal Article
• Authors: Johnson, Stuart L.; Wedemeyer, Carolina; Vetter, Douglas E.; Adachi, Roberto; Holley, Matthew C.; Elgoyhen, Ana Belén; Marcotti, Walter
• Is Part Of: Open biology. Volume 3:Issue 11(2013)
• Publication Date: 2013-11
• Subjects: hair cell -- development -- cochlea -- calcium current -- exocytosis -- efferent system; Biology -- Periodicals; 570
• DOI: 10.1098/rsob.130163
• Languages: English
• ISSNs: 2046-2441

Abstract

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.