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Position-dependent patterning of spontaneous action potentials in immature cochlear inner hair cells

Nature Neuroscience volume 14, pages 711–717 (2011)Cite this article

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Abstract

Spontaneous action potential activity is crucial for mammalian sensory system development. In the auditory system, patterned firing activity has been observed in immature spiral ganglion and brain-stem neurons and is likely to depend on cochlear inner hair cell (IHC) action potentials. It remains uncertain whether spiking activity is intrinsic to developing IHCs and whether it shows patterning. We found that action potentials were intrinsically generated by immature IHCs of altricial rodents and that apical IHCs showed bursting activity as opposed to more sustained firing in basal cells. We show that the efferent neurotransmitter acetylcholine fine-tunes the IHC's resting membrane potential (Vm), and as such is crucial for the bursting pattern in apical cells. Endogenous extracellular ATP also contributes to the Vm of apical and basal IHCs by triggering small-conductance Ca2+-activated K+ (SK2) channels. We propose that the difference in firing pattern along the cochlea instructs the tonotopic differentiation of IHCs and auditory pathway.

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Figure 1: Cell-attached spikes result from spontaneous action potentials.
Figure 2: Spontaneous action potentials in IHCs require physiological recording conditions.
Figure 3: Patterning of spontaneous spiking activity in apical and basal IHCs.
Figure 4: Modulation of action potential activity of mouse IHCs by superfusing ATP.
Figure 5: Role of endogenous ATP in spontaneous spiking activity in mouse IHCs.
Figure 6: Dual action of ATP on spontaneous spiking activity in mouse IHCs.
Figure 7: Effect of endogenous ACh on IHC spontaneous spiking activity.

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Acknowledgements

This work was supported by project grants from the Wellcome Trust (088719), the Royal National Institute for Deaf People (G41) and Deafness Research UK to W.M. and a Medical Research Council Programme Grant (G0100798) to C.J.K. SK2-knockout mice were obtained from J.P. Adelman. W.M. is a Royal Society University Research Fellow.

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Authors and Affiliations

  1. Department of Biomedical Science, University of Sheffield, Sheffield, UK

    Stuart L Johnson, Tobias Eckrich, Stephanie Kuhn, Valeria Zampini & Walter Marcotti

  2. Department of Physiology, University of Pavia, Pavia, Italy

    Valeria Zampini & Sergio Masetto

  3. Department of Otolaryngology, Tübingen Hearing Research Center, Laboratory of Molecular Physiology of Hearing, University of Tübingen, Tübingen, Germany

    Christoph Franz & Marlies Knipper

  4. School of Life Sciences, University of Sussex, Falmer, Brighton, UK

    Kishani M Ranatunga, Terri P Roberts & Corné J Kros

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Contributions

S.L.J. and W.M. performed most of the experimental work. All authors helped with the collection and analysis of the electrophysiological data. C.F. and M.K. collected immunolabeling data. C.J.K. had the initial idea of using cell-attached recording of IHC action potentials. W.M., S.L.J. and C.J.K. designed the experiments and wrote the paper. All authors discussed the results and commented on the manuscript.

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Correspondence to Corné J Kros or Walter Marcotti.

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The authors declare no competing financial interests.

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Johnson, S., Eckrich, T., Kuhn, S. et al. Position-dependent patterning of spontaneous action potentials in immature cochlear inner hair cells. Nat Neurosci 14, 711–717 (2011). https://doi.org/10.1038/nn.2803

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