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

Stuart L. Johnson, Stephanie Kuhn, Christoph Franz, Neil Ingham, David N. Furness, Marlies Knipper, Karen P. Steel, John P. Adelman, Matthew C. Holley, Walter Marcotti

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


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 unknownwhether 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.

Original languageEnglish (US)
Pages (from-to)8720-8725
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number21
StatePublished - May 21 2013
Externally publishedYes


  • Calcium current
  • Cochlea
  • Exocytosis
  • Kcnn2

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Presynaptic maturation in auditory hair cells requires a critical period of sensory-independent spiking activity'. Together they form a unique fingerprint.

Cite this