Loss and Regeneration of Cochlear Hair Cell Innervation Following Sound and Drug Damage

Abstract

In bird cochleae, sound damage and aminoglycoside treatment result in a localized loss of hair cells from the basilar papilla. This loss induces a structural regeneration of hair cells that leads to the recovery of hearing function. However, little is known about the damage to and repair of nerves connecting the hair cells with the auditory CNS. We have employed whole-mount immunocytochemical labeling of normal, sound-damaged, and gentamicin-treated cochleae to localize neuron-specific proteins at distinct sites within the nerve fibers and the nerve terminals before and after damage. Neurofilament antibodies label both afferent and efferent nerve fibers in the basilar papilla and demonstrate that nerve processes ramifying throughout the sensory epithelium are not significantly damaged by moderate sound damage or gentamicin treatment. Labeling of efferent terminals for synapsin, choline acetyltransferase, and syntaxin reveals differences in damage to the terminals after sound damage versus gentamicin treatment. The entire efferent terminal is extruded after sound damage, leaving little synaptic protein in the basilar papilla. However, after gentamicin damage, the terminal breaks apart, with the syntaxin-labeled presynaptic membrane extruded on the hair cells while the fragments of the terminal containing synapsin and ChAT remain within the basilar papilla. Regeneration of the efferent terminals is significantly delayed following gentamicin treatment relative to the recovery after sound damage. Most regenerated short hair cells exhibit large cup-like efferent terminals within two weeks after sound exposure. In contrast,only about 50% of the new hair cells exhibit cup-like endings 60 days affer gentamicin treatment.