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 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 IHC synaptic machinery. The central control of sensory cell development is unique among sensory systems.
Highlights
Hearing in mammals depends on temporally precise neurotransmission via the ribbon synapses between inner hair cells (IHCs) and auditory afferent nerve terminals [1]
In immature IHCs, the ACh-activated current is mediated by Ca2þ entering hair cells through a9a10nAChRs [27,28], which a9-nicotinic acetylcholine receptor subunit (a9nAChR) (P15–32)
We found no evidence for a change in spontaneous ACh release from efferent terminals based on the normal action potential frequency in immature IHCs and size of spontaneous inhibitory postsynaptic potentials (IPSPs; control: 6.6 + 0.2 pA, 66 events from six IHCs; Synaptotagmin 2 (Syt-2) KO: 6.4 + 0.2 pA, 69 events from seven IHCs, arrows in figure 3a)
Summary
Hearing in mammals depends on temporally precise neurotransmission via the ribbon synapses between inner hair cells (IHCs) and auditory afferent nerve terminals [1]. In order to become so highly specialized, immature spiking IHCs undergo a number of developmental transitions such that their properties change almost completely at around the onset of hearing [2], which is at postnatal day 12. License http://creativecommons.org/licenses/by/3.0/, which permits unrestricted use, provided the original author and source are credited. (a) a9nAChR control (b) a9nAChR KO 1 mM ACh. 100 pA 2s (c) 30 mM KCl (d) 30 mM KCl Vm (mV) Vm (mV) (e) 5s (f) 30 mM ACh pA
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
