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.

Differential expression of P2Y receptors in the rat cochlea during development

“…Study of the neonatal rat organ of Corti has also revealed spontaneous pulsatile ATP release from the columnar epithelial cells of the transient Kölliker's organ (greater epithelial ridge), located medial to the inner hair cells [2]. The release mechanism is likely to engage the same extracellular ATP-mediated ATP release process and has Fig.…”

“…b P2Y 4 immunolabeling was only present on the sensory epithelium and greater epithelial ridge (arrowheads). c P2Y 6 [2] differentiates into the inner sulcus region. P2Y 4 expression is pronounced here (Figs.…”

“…7d,e). The heads of the pillar cells, facing scala media expressed P2Y 2 (Figs. 6b and 7b) and P2Y 6 (Figs.…”

“…A purinergic signaling mechanism underlies this process which involves release of ATP from epithelial cells within the transient Kölliker's organ (greater epithelial ridge), part of the developing auditory sensory organ. Extracellular ATP activates P2 receptors on the inner hair cells causing depolarization and glutamatergic neurotransmission to the spiral ganglion neurons [2]. Both P2X receptors (ATP-gated ion channels and P2Y (G-protein-coupled) receptors are implicated.…”

Reduced P2x2 receptor-mediated regulation of endocochlear potential in the ageing mouse cochlea

“…Purinergic signalling appears to be involved in the regulation of hearing sensitivity under stress conditions, acting via the P2X 2 subtype of the receptor in tissues lining the endolymphatic compartment [2,5]. There is increasing evidence that ATP is a neuromodulator at the primary synapse between the inner hair cell and auditory afferent neurones [6] and is a neurotransmitter at the type II synapse with the outer hair cells [7] which regulates the generation of spontaneous neural activity in the developing cochlea [8]. ATP acts as a vasoactive signal, regulating cochlear blood flow [9], and appears to be involved in regulating cochlear mechanics via an action on the Deiters' supporting cells of the auditory sensory organ [10][11][12].…”