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 Adelman, Matthew C. Holley, Walter Marcotti

Research output: Contribution to journalArticle

42 Citations (Scopus)

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 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
Volume110
Issue number21
DOIs
StatePublished - May 21 2013

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Inner Auditory Hair Cells
Auditory Hair Cells
Synapses
Action Potentials
Calcium Signaling
Doxycycline
Potassium Channels
Calcium

Keywords

  • Calcium current
  • Cochlea
  • Exocytosis
  • Kcnn2

ASJC Scopus subject areas

  • General

Cite this

Presynaptic maturation in auditory hair cells requires a critical period of sensory-independent spiking activity. / Johnson, Stuart L.; Kuhn, Stephanie; Franz, Christoph; Ingham, Neil; Furness, David N.; Knipper, Marlies; Steel, Karen P.; Adelman, John; Holley, Matthew C.; Marcotti, Walter.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 21, 21.05.2013, p. 8720-8725.

Research output: Contribution to journalArticle

Johnson, SL, Kuhn, S, Franz, C, Ingham, N, Furness, DN, Knipper, M, Steel, KP, Adelman, J, Holley, MC & Marcotti, W 2013, 'Presynaptic maturation in auditory hair cells requires a critical period of sensory-independent spiking activity', Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 21, pp. 8720-8725. https://doi.org/10.1073/pnas.1219578110
Johnson, Stuart L. ; Kuhn, Stephanie ; Franz, Christoph ; Ingham, Neil ; Furness, David N. ; Knipper, Marlies ; Steel, Karen P. ; Adelman, John ; Holley, Matthew C. ; Marcotti, Walter. / Presynaptic maturation in auditory hair cells requires a critical period of sensory-independent spiking activity. In: Proceedings of the National Academy of Sciences of the United States of America. 2013 ; Vol. 110, No. 21. pp. 8720-8725.
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