title: Functional recovery of hearing following ampa-induced reversible disruption of hair cell afferent synapses in the avian inner ear.
abstract: Hair cells in the avian inner ear can regenerate after acoustic trauma or ototoxic insult, and significant functional recovery from hearing loss occurs. However, small residual deficits remain, possibly as a result of incomplete reestablishment of the hair cell neural synaptic contacts. The aim of the present study was to determine if intracochlear application of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), an excitotoxic glutamate agonist, causes reversible disruption of hair cell neural contacts in the bird, and to what extent functional recovery occurs if synaptic contacts are reestablished. Compound action potential (CAP) responses to tone bursts were recorded to determine hearing thresholds during a recovery period of up to 4 months. Subsequently, the response properties of single auditory nerve fibers were analyzed in the same animals. Instillation of AMPA into the perilymph of the scala tympani led to immediate abolition of CAP thresholds. Partial recovery occurred over a period of 2-3 weeks, without further improvement of thresholds thereafter. High-frequency thresholds did not reach control values even after 3-4 months of recovery. Single-ganglion cell response properties, obtained 3-4 months after AMPA treatment, showed elevated thresholds at the fiber's characteristic frequency (CF) for units with CF above 0.3 kHz. Sharpness of tuning (Q(10 dB)) was reduced in units with CF above 0.4 kHz. The spontaneous firing rate was higher in units with CF above 0.18 kHz. The maximum sound-evoked discharge rate was also increased. Transmission electron micrographs of the basilar papilla showed that, following AMPA treatment, the nerve endings went through a sequence of swelling, degeneration and recovery over a period of 3-7 days. The process of neosynaptogenesis was completed 14 days after exposure. The present findings are strong evidence for a role of glutamate or a related excitatory amino acid as the afferent transmitter in the avian inner ear. In addition they show that functional recovery after disruption and regeneration of hair cell neural synapses, without apparent damage to the hair cells, is incomplete.
authors.affiliation: Physiologisches Institut II, Klinikum der J.W.-Goethe-Universität, Frankfurt am Main, Deutschland.
authors.forename: D
authors.initials: D
authors.lastname: Reng
authors.forename: M
authors.initials: M
authors.lastname: Müller
authors.forename: J W
authors.initials: JW
authors.lastname: Smolders
mesh_terms: D000818:Animals; D001309:Auditory Threshold / Q000502:physiology; D003051:Cochlea / Q000187:drug effects / Q000648:ultrastructure; D003056:Cochlear Nerve / Q000187:drug effects / Q000648:ultrastructure; D010856:Columbidae; D007758:Ear, Inner / Q000187:drug effects* / Q000502:physiology*; D004567:Electrodes, Implanted; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D006309:Hearing / Q000187:drug effects* / Q000502:physiology*; D009412:Nerve Fibers / Q000187:drug effects / Q000648:ultrastructure; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D020127:Recovery of Function; D013569:Synapses / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D013997:Time Factors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000009:adverse effects*
chemical_list: D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid