Cholinergic efferent synaptic transmission regulates the maturation of auditory hair cell ribbon synapses

JOHNSON SL; WEDEMEYER C; VETTER D; ADACHI R; HOLLEY MC; ELGOYHEN AB; MARCOTTI W

Open Biology

Royal Society

Año: 2013 vol. 3 p. 1130163 - 1130163

2046-2441

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 a9-nicotinic acetylcholine receptor subunit (a9nAChR) 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 Ca2+-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 IHCs synaptic machinery. This central control of development is unique amongst sensory systems.