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Proc Natl Acad Sci U S A. 2013 May 21;110(21):8720-5. doi: 10.1073/pnas.1219578110. Epub 2013 May 6.

Presynaptic maturation in auditory hair cells requires a critical period of sensory-independent spiking activity.

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Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, United Kingdom.


The development of neural circuits relies on spontaneous electrical activity that occurs during immature stages of development. In the developing mammalian auditory system, spontaneous calcium action potentials are generated by inner hair cells (IHCs), which form the primary sensory synapse. It remains unknown whether this electrical activity is required for the functional maturation of the auditory system. We found that sensory-independent electrical activity controls synaptic maturation in IHCs. We used a mouse model in which the potassium channel SK2 is normally overexpressed, but can be modulated in vivo using doxycycline. SK2 overexpression affected the frequency and duration of spontaneous action potentials, which prevented the development of the Ca(2+)-sensitivity of vesicle fusion at IHC ribbon synapses, without affecting their morphology or general cell development. By manipulating the in vivo expression of SK2 channels, we identified the "critical period" during which spiking activity influences IHC synaptic maturation. Here we provide direct evidence that IHC development depends upon a specific temporal pattern of calcium spikes before sound-driven neuronal activity.


calcium current; cochlea; exocytosis; kcnn2

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