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The origin of spontaneous activity in the developing auditory system

Abstract

Spontaneous activity in the developing auditory system is required for neuronal survival as well as the refinement and maintenance of tonotopic maps in the brain. However, the mechanisms responsible for initiating auditory nerve firing in the absence of sound have not been determined. Here we show that supporting cells in the developing rat cochlea spontaneously release ATP, which causes nearby inner hair cells to depolarize and release glutamate, triggering discrete bursts of action potentials in primary auditory neurons. This endogenous, ATP-mediated signalling synchronizes the output of neighbouring inner hair cells, which may help refine tonotopic maps in the brain. Spontaneous ATP-dependent signalling rapidly subsides after the onset of hearing, thereby preventing this experience-independent activity from interfering with accurate encoding of sound. These data indicate that supporting cells in the organ of Corti initiate electrical activity in auditory nerves before hearing, pointing to an essential role for peripheral, non-sensory cells in the development of central auditory pathways.

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Figure 1: Spontaneous purinergic signalling in the developing cochlea.
Figure 2: ATP release elicits optical changes and intercellular Ca 2+ waves in Kölliker’s organ.
Figure 3: Supporting-cell-derived ATP depolarizes IHCs.
Figure 4: Supporting-cell-derived ATP triggers bursts of action potentials in auditory nerve fibres.
Figure 5: Intrinsic purinergic signalling ceases after the onset of hearing.
Figure 6: Local release of ATP synchronizes the activity of neighbouring IHCs.

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Acknowledgements

We thank J.-H. Kong for help with preliminary experiments, and P. Fuchs, J. Howell and M. Lahne for discussions. This work was supported by a Royal Society University Research Fellowship (to J.E.G.), National Institutes of Health Grants (to E.G. and D.E.B.) and the Deafness Research Foundation (to D.E.B.).

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Correspondence to Dwight E. Bergles.

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Supplementary information

Supplementary Figures

The file contains Supplementary Figures 1-6 with Legends and Supplementary Video Legends. Supplementary Figures 1-6 and their legends provide evidence for correlation between spontaneous field potentials and inward currents in supporting cells, additional pharmacology of spontaneous extracellular potentials and spontaneous inward currents in supporting cells and inner hair cells, and further characterization of spontaneous optical changes and ATP-elicited Ca2+ transients within the developing cochlea. (PDF 12570 kb)

Supplementary Video 1a

The file contains Supplementary Video 1a showing time lapse of the unprocessed transmitted light (IR-DIC) signal acquired from a P8 rat organ of Corti illustrates the intrinsic optical changes that spontaneously occur in the supporting cells of Kölliker’s organ. (MOV 6687 kb)

Supplementary Video 1b

The file contains Supplementary Video 1b showing time lapse of Supplementary Video 1 after image subtraction, providing an index of transmitted light change over time. (MOV 10102 kb)

Supplementary Video 1c

The file contains Supplementary Video 1c showing time lapse of Supplementary Video 1 after image subtraction, thresholding and pseudocoloring. (MOV 2499 kb)

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Tritsch, N., Yi, E., Gale, J. et al. The origin of spontaneous activity in the developing auditory system. Nature 450, 50–55 (2007). https://doi.org/10.1038/nature06233

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