Central nervous system plasticity during hair cell loss and regeneration.
Following cochlear ablation, auditory neurons in the central nervous system (CNS) undergo alterations in morphology and function, including neuronal cell death. The trigger for these CNS changes is the abrupt cessation of afferent input via eighth nerve fiber activity. Gentamicin can cause ototoxic damage to cochlear hair cells responsible for high frequency hearing, which seems likely to cause a frequency-specific loss of input into the CNS. In birds, these hair cells can regenerate, presumably restoring input into the CNS. This review summarizes current knowledge of how CNS auditory neurons respond to this transient, frequency-specific loss of cochlear function. A single systemic injection of a high dose of gentamicin results in the complete loss of high frequency hair cells by 5 days, followed by the regeneration of new hair cells. Both hair cell-specific functional measures and estimates of CNS afferent activity suggest that newly regenerated hair cells restore afferent input to brainstem auditory neurons. Frequency-specific neuronal cell death and shrinkage occur following gentamicin damage to hair cells, with an unexpected recovery of neuronal cell number at longer survival times. A newly-developed method for topical, unilateral gentamicin application will allow future studies to compare neuronal changes within a given animal.
Durham
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Department of Otolaryngology and the Smith Mental Retardation and Human Development Research Center, University of Kansas Medical Center, Kansas City 66160-7380, USA. ddurham@kumc.edu
Park
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Girod
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D000818:Animals; D001306:Auditory Pathways / Q000502:physiology; D020532:Basal Nucleus of Meynert / Q000502:physiology; D002645:Chickens; D003714:Denervation; D005839:Gentamicins / Q000633:toxicity; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000502:physiology*; D008855:Microscopy, Electron, Scanning; D009473:Neuronal Plasticity; D017084:Otoacoustic Emissions, Spontaneous; D012038:Regeneration
D005839:Gentamicins