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

Greenwood, D; Jagger, DJ; Huang, LC; Hoya, N; Thorne, PR; Wildman, SS; King, BF; ... Housley, GD; + view all (2007) P2X receptor signaling inhibits BDNF-mediated spiral ganglion neuron development in the neonatal rat cochlea. DEVELOPMENT , 134 (7) 1407 - 1417. 10.1242/dev.002279.

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Abstract

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 P2X(3), 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 P2X(3) 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 ATP gamma S or alpha,beta MeATP 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.

Type: Article
Title: P2X receptor signaling inhibits BDNF-mediated spiral ganglion neuron development in the neonatal rat cochlea
DOI: 10.1242/dev.002279
Keywords: spiral ganglion neuron, ATP-gated ion channel, neurotrophins, BDNF, synaptic reorganization, afferent development, 5'-TRIPHOSPHATE-GATED ION-CHANNEL, PRIMARY AUDITORY NEURONS, ATP-GATED CURRENTS, TIME RT-PCR, SINGLE-CELL, SENSORY NEURONS, INNER-EAR, STRUCTURAL MOTIF, EXPRESSION, SUBUNIT
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/164224
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