Purinergic signaling controls spontaneous activity in the auditory system throughout early development

Travis A. Babola, Sally Li, Zhirong Wang, Calvin J. Kersbergen, Ana Belén Elgoyhen, Thomas M. Coate, Dwight E. Bergles

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Spontaneous bursts of electrical activity in the developing auditory system arise within the cochlea before hearing onset and propagate through future sound-processing circuits of the brain to promote maturation of auditory neurons. Studies in isolated cochleae revealed that this intrinsically generated activity is initiated by ATP release from inner supporting cells (ISCs), resulting in activation of purinergic autoreceptors, K+ efflux, and subsequent depolarization of inner hair cells. However, it is unknown when this activity emerges or whether different mechanisms induce activity during distinct stages of development. Here we show that spontaneous electrical activity in mouse cochlea from both sexes emerges within ISCs during the late embryonic period, preceding the onset of spontaneous correlated activity in inner hair cells and spiral ganglion neurons, which begins at birth and follows a base to apex developmental gradient. At all developmental ages, pharmacological inhibition of P2Y1 purinergic receptors dramatically reduced spontaneous activity in these three cell types. Moreover, in vivo imaging within the inferior colliculus revealed that auditory neurons within future isofrequency zones exhibit coordinated neural activity at birth. The frequency of these discrete bursts increased progressively during the postnatal prehearing period yet remained dependent on P2RY1. Analysis of mice with disrupted cholinergic signaling in the cochlea indicate that this efferent input modulates, rather than initiates, spontaneous activity before hearing onset. Thus, the auditory system uses a consistent mechanism involving ATP release from ISCs and activation of P2RY1 autoreceptors to elicit coordinated excitation of neurons that will process similar frequencies of sound.

Original languageEnglish (US)
Pages (from-to)594-612
Number of pages19
JournalJournal of Neuroscience
Issue number4
StatePublished - Jan 27 2021


  • A9
  • Cochlea
  • Inferior colliculus
  • P2RY1
  • Potassium buffering
  • Purinergic

ASJC Scopus subject areas

  • Neuroscience(all)


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