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Published on: November 26, 2015
Patterns of cell death in mouse anteroventral cochlear nucleus neurons after unilateral cochlea removal
S P Mostafapour1, S L Cochran, N M Del Puerto
1Virginia Merrill Bloedel Hearing Research Center and Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, Washington 98195, USA.
Abstract:
Developmental changes that influence the results of removal of afferent input on the survival of neurons of the anteroventral cochlear nucleus (AVCN) of mice were examined with the hope of providing a suitable model for understanding the cellular and molecular basis for these developmental changes in susceptibility. We performed unilateral cochlear ablation on wild-type mice at a variety of ages around the time of hearing onset to determine developmental changes in the sensitivity of AVCN neurons to afferent deprivation. In postnatal day 5 (P5) mice, cochlea removal resulted in 61% neuronal loss in the AVCN. By age P14, fewer than 1% of AVCN neurons were lost after this manipulation. This reveals a rather abrupt change in the sensitivity to disruption of afferent input, a critical period. We next investigated the temporal events associated with neuron loss after cochlea removal in susceptible animals. We demonstrate that significant cell loss occurs within 48 hours of cochlea removal in P7 animals. Furthermore, evidence of apoptosis was observed within 12 hours of cochlea removal, suggesting that the molecular events leading to cell loss after afferent deprivation begin to occur within hours of cochlea removal. Finally, we began to examine the role of the bcl-2 gene family in regulating afferent deprivation-induced cell death in the mouse AVCN. AVCN neurons in mature bcl-2 knockout mice demonstrate susceptibility to removal of afferent input comparable to neonatal sensitivity of wild-type controls. These data suggest that bcl-2 is one effector of cell survival as these cells switch from afferent-dependent to -independent survival mechanisms.
Insights
Neuronal survival in the anteroventral cochlear nucleus (AVCN) shows a critical developmental window of heightened sensitivity to afferent deprivation in mice. This sensitivity is linked to the bcl-2 gene family, influencing survival mechanisms.
Area of Science:
- Neuroscience
- Developmental Biology
- Auditory System Research
Background:
- The survival of neurons in the anteroventral cochlear nucleus (AVCN) is influenced by afferent input during development.
- Understanding the cellular and molecular basis of developmental changes in neuronal susceptibility is crucial for auditory system research.
Purpose of the Study:
- To investigate developmental changes in the sensitivity of AVCN neurons to afferent deprivation in mice.
- To establish a model for studying the cellular and molecular mechanisms underlying developmental changes in neuronal susceptibility.
- To examine the role of the bcl-2 gene family in regulating cell death following afferent deprivation.
Main Methods:
- Unilateral cochlear ablation was performed on wild-type mice at various ages around hearing onset.
- Temporal events of neuron loss and apoptosis were analyzed in susceptible animals (P7 mice) post-ablation.
- AVCN neurons from mature bcl-2 knockout mice were assessed for susceptibility to afferent input removal.
Main Results:
- Cochlea removal in postnatal day 5 (P5) mice led to 61% AVCN neuronal loss, drastically reducing to <1% by P14, indicating a critical period.
- Significant cell loss occurred within 48 hours, with apoptosis observed within 12 hours of cochlea removal in P7 mice.
- Mature bcl-2 knockout mice showed AVCN neuron susceptibility to afferent deprivation similar to neonatal wild-type mice.
Conclusions:
- A critical developmental period exists where AVCN neurons are highly susceptible to afferent deprivation.
- The molecular events triggering cell loss after afferent deprivation begin rapidly, within hours of input removal.
- The bcl-2 gene family plays a role in AVCN neuron survival during the transition from afferent-dependent to -independent mechanisms.
