Related Experiment Videos
Central nervous system plasticity during hair cell loss and regeneration
D Durham1, D L Park, D A Girod
1Department 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
Abstract:
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.
Insights
Auditory neurons in the central nervous system (CNS) change after cochlear hair cell damage. Regenerated hair cells can restore neural input, leading to unexpected recovery of neuron numbers.
Area of Science:
- Neuroscience
- Auditory system research
- Ototoxicity studies
Background:
- Cochlear ablation and afferent input cessation trigger central nervous system (CNS) auditory neuron changes.
- Gentamicin-induced ototoxicity damages high-frequency cochlear hair cells, causing frequency-specific input loss.
- Hair cell regeneration in birds may restore CNS auditory input.
Purpose of the Study:
- To review CNS auditory neuron responses to transient, frequency-specific cochlear function loss.
- To understand the impact of gentamicin-induced hair cell damage and regeneration on auditory neurons.
- To explore recovery mechanisms in the central auditory system.
Main Methods:
- Review of existing literature on gentamicin's effects on cochlear hair cells and CNS auditory neurons.
- Analysis of studies investigating afferent activity and neuronal changes post-ototoxicity.
- Consideration of newly developed methods for localized ototoxic application.
Main Results:
- Systemic gentamicin causes high-frequency hair cell loss, followed by regeneration and restored afferent input.
- Frequency-specific neuronal cell death and shrinkage occur after hair cell damage.
- Unexpected recovery of neuronal cell numbers is observed at later time points.
Conclusions:
- Transient, frequency-specific cochlear input loss induces significant CNS auditory neuron alterations.
- Regenerated hair cells can functionally restore afferent input to brainstem auditory neurons.
- The CNS auditory system exhibits a capacity for recovery following ototoxic insult.