title: Reduced sensory stimulation alters the molecular make-up of glutamatergic hair cell synapses in the developing cochlea.
abstract: Neural activity during early development is known to alter innervation pathways in the central and peripheral nervous systems. We sought to examine how reduced sound-induced sensory activity in the cochlea affected the consolidation of glutamatergic synapses between inner hair cells (IHC) and the primary auditory neurons as these synapses play a primary role in transmitting sound information to the brain. A unilateral conductive hearing loss was induced prior to the onset of sound-mediated stimulation of the sensory hair cells, by rupturing the tympanic membrane and dislocating the auditory ossicles in the left ear of P11 mice. Auditory brainstem responses at P15 and P21 showed a 40-50-dB increase in thresholds for frequencies 8-32kHz in the dislocated ear relative to the control ear. Immunohistochemistry and confocal microscopy were subsequently used to examine the effect of this attenuation of sound stimulation on the expression of RIBEYE, which comprises the presynaptic ribbons, Shank-1, a postsynaptic scaffolding protein, and the GluA2/3 and 4 subunits of postsynaptic AMPA receptors. Our results show that dislocation did not alter the number of pre- or postsynaptic protein puncta. However, dislocation did increase the size of RIBEYE, GluA4, GluA2/3 and Shank-1 puncta, with postsynaptic changes preceding presynaptic changes. Our data suggest that a reduction in sound stimulation during auditory development induces plasticity in the molecular make-up of IHC glutamatergic synapses, but does not affect the number of these synapses. Up-regulation of synaptic proteins with sound attenuation may facilitate a compensatory increase in synaptic transmission due to the reduced sensory stimulation of the IHC.
authors.affiliation: Department of Physiology and Centre for Brain Research, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: M
authors.initials: M
authors.lastname: Barclay
authors.affiliation: Department of Physiology and Centre for Brain Research, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: R
authors.initials: R
authors.lastname: Constable
authors.affiliation: Department of Physiology and Centre for Brain Research, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: N R
authors.initials: NR
authors.lastname: James
authors.affiliation: Department of Physiology and Centre for Brain Research, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand; Section of Audiology, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: P R
authors.initials: PR
authors.lastname: Thorne
authors.affiliation: Department of Physiology and Centre for Brain Research, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand. Electronic address: jm.montgomery@auckland.ac.nz.
authors.forename: J M
authors.initials: JM
authors.lastname: Montgomery
mesh_terms: D000161:Acoustic Stimulation; D000429:Alcohol Oxidoreductases; D000818:Animals; D001306:Auditory Pathways / Q000254:growth & development / Q000378:metabolism; D056970:Co-Repressor Proteins; D003051:Cochlea / Q000254:growth & development*; D004268:DNA-Binding Proteins / Q000378:metabolism; D016057:Evoked Potentials, Auditory, Brain Stem; D006199:Hair Cells, Auditory, Inner / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism*; D018091:Receptors, AMPA / Q000378:metabolism*; D012683:Sensory Deprivation; D013136:Spiral Ganglion / Q000254:growth & development / Q000378:metabolism*
chemical_list: D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D018091:Receptors, AMPA; C512412:SHANK1 protein, mouse; D000429:Alcohol Oxidoreductases; C111341:Ctbp2 protein, mouse
keywords: cochlea; conductive deafness; development; glutamate; spiral ganglion neurons; synapses