title: Presynaptic maturation in auditory hair cells requires a critical period of sensory-independent spiking activity.
abstract: 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.
authors: Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, United Kingdom.
authors: Stuart L
authors: SL
authors: Johnson
authors: Stephanie
authors: S
authors: Kuhn
authors: Christoph
authors: C
authors: Franz
authors: Neil
authors: N
authors: Ingham
authors: David N
authors: DN
authors: Furness
authors: Marlies
authors: M
authors: Knipper
authors: Karen P
authors: KP
authors: Steel
authors: John P
authors: JP
authors: Adelman
authors: Matthew C
authors: MC
authors: Holley
authors: Walter
authors: W
authors: Marcotti
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D004318:Doxycycline / Q000494:pharmacology; D006199:Hair Cells, Auditory, Inner / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D051640:Small-Conductance Calcium-Activated Potassium Channels; D004318:Doxycycline; D002118:Calcium
keywords: calcium current; cochlea; exocytosis; kcnn2
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