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First published online 28 February 2007
doi: 10.1242/dev.002279

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P2X receptor signaling inhibits BDNF-mediated spiral ganglion neuron development in the neonatal rat cochlea

¹ Department of Physiology, University of Auckland, Private Bag 92019, Auckland, New Zealand.
² Centre for Auditory Research, University College London, London, UK.
³ Audiology Discipline, University of Auckland, Private Bag 92019, Auckland, New Zealand.
⁴ Department of Physiology, University College Medical School, University College London, London, UK.
⁵ Departments of Surgery, University of California, San Diego, 9500 Gilman Drive, La Jolla, San Diego, CA 92093, USA.
⁶ Departments of Neuroscience, University of California, San Diego, 9500 Gilman Drive, La Jolla, San Diego, CA 92093, USA.

^* Author for correspondence (e-mail: g.housley{at}auckland.ac.nz)

Accepted 31 January 2007

Type I and type II spiral ganglion neurons (SGN) innervate the inner and outer hair cells of the cochlea, respectively. This neural system is established by reorganization of promiscuous innervation of the hair cells, immediately before hearing is established. The mechanism for this synaptic reorganization is unresolved but probably includes regulation of trophic support between the hair cells and the neurons. We provide evidence that P2X receptors (ATP-gated ion channels) contribute such a mechanism in the neonatal rat cochlea. Single-cell quantitative RT-PCR identified the differential expression of two P2X receptor subunits, splice variant P2X_2-3 and P2X₃, in a 1:2 transcript ratio. Downregulation of this P2X_2-3/3 receptor coincided with maturation of the SGN innervation of the hair cells. When the P2X_2-3 and P2X₃ subunits were co-expressed in Xenopus oocytes, the resultant P2X receptor properties corresponded to the SGN phenotype. This included enhanced sensitivity to ATP and extended agonist action. In P4 spiral ganglion explants, activation of the P2X receptor signaling pathway by ATPS or ,ßMeATP inhibited BDNF-induced neurite outgrowth and branching. These findings indicate that P2X receptor signaling provides a mechanism for inhibiting neurotrophin support of SGN neurites when synaptic reorganization is occurring in the cochlea.

Key words: Spiral ganglion neuron, ATP-gated ion channel, Neurotrophins, BDNF, Synaptic reorganization, Afferent development

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