Purinergic modulation of neuronal activity in developing auditory brainstem

J Neurosci. 2012 Aug 1;32(31):10699-712. doi: 10.1523/JNEUROSCI.0372-12.2012.


In the developing nervous system, spontaneous neuronal activity arises independently of experience or any environmental input. This activity may play a major role in axonal pathfinding, refinement of topographic maps, dendritic morphogenesis, and the segregation of axonal terminal arbors. In the auditory system, endogenously released ATP in the cochlea activates inner hair cells to trigger bursts of action potentials (APs), which are transferred to the central auditory system. Here we show the modulatory role of purinergic signaling beyond the cochlea, i.e., the developmentally regulated and cell-type-specific depolarizing effects on auditory brainstem neurons of Mongolian gerbil. We assessed the effects of P2X receptors (P2XRs) on neuronal excitability from prehearing to early stages of auditory signal processing. Our results demonstrate that in neurons expressing P2XRs, extracellular ATP can evoke APs in sync with Ca(2+) signals. In cochlear nucleus (CN) bushy cells, ATP increases spontaneous and also acoustically evoked activity in vivo, but these effects diminish with maturity. Moreover, ATP not only augmented glutamate-driven firing, but it also evoked APs in the absence of glutamatergic transmission. In vivo recordings also revealed that endogenously released ATP in the CN contributes to neuronal firing activity by facilitating AP generation and prolonging AP duration. Given the enhancing effect of ATP on AP firing and confinement of P2XRs to certain auditory brainstem nuclei, and to distinct neurons within these nuclei, it is conceivable that purinergic signaling plays a specific role in the development of neuronal brainstem circuits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / metabolism
  • Adenosine Triphosphate / pharmacology
  • Age Factors
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Brain Stem / cytology*
  • Brain Stem / growth & development*
  • Calcium / metabolism
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Electric Stimulation
  • Excitatory Amino Acid Antagonists / pharmacology
  • Female
  • Gerbillinae
  • Glycine / pharmacology
  • In Vitro Techniques
  • Kynurenic Acid / pharmacology
  • Male
  • Patch-Clamp Techniques
  • Psychoacoustics
  • Receptors, Purinergic P2X / metabolism*
  • Sensory Receptor Cells / drug effects
  • Sensory Receptor Cells / physiology*
  • Signal Transduction / drug effects
  • Stilbamidines / metabolism
  • Synaptic Potentials / drug effects


  • 2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt
  • Excitatory Amino Acid Antagonists
  • Receptors, Purinergic P2X
  • Stilbamidines
  • adenosine 5'-O-(3-thiotriphosphate)
  • 2',3'-O-(2,4,6-trinitro-cyclohexadienylidine)adenosine 5'-triphosphate
  • Adenosine Triphosphate
  • Kynurenic Acid
  • Calcium
  • Glycine