title: Cholinergic efferent synaptic transmission regulates the maturation of auditory hair cell ribbon synapses.
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.
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Johnson
authors.forename: Carolina
authors.initials: C
authors.lastname: Wedemeyer
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Vetter
authors.forename: Roberto
authors.initials: R
authors.lastname: Adachi
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Holley
authors.forename: Ana Belén
authors.initials: AB
authors.lastname: Elgoyhen
authors.forename: Walter
authors.initials: W
authors.lastname: Marcotti
mesh_terms: D000200:Action Potentials; D000818:Animals; D003051:Cochlea / Q000502:physiology; D006199:Hair Cells, Auditory, Inner / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology*; D059547:Stereocilia; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D050861:Synaptotagmin II / Q000235:genetics / Q000502:physiology
chemical_list: C402445:Chrna9 protein, mouse; D011978:Receptors, Nicotinic; D050861:Synaptotagmin II; C494263:Syt2 protein, mouse