Patterns of cell death in mouse anteroventral cochlear nucleus neurons after unilateral cochlea removal

Developmental changes that influence the results of removal of afferent inp ut on the survival of neurons of the anteroventral cochlear nucleus (AVCN) of mice were examined with the hope of providing a suitable model for under standing the cellular and molecular basis for these developmental changes i n susceptibility. We performed unilateral cochlear ablation on wild-type mi ce at a variety of ages around the time of hearing onset to determine devel opmental changes in the sensitivity of AVCN neurons to afferent deprivation . In postnatal day 5 (P5) mice, cochlea removal resulted in 61% neuronal lo ss in the AVCN. By age P14, fewer than 1% of AVCN neurons were lost after t his 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 suscep tible animals. We demonstrate that significant cell loss occurs within 48 h ours of cochlea removal in P7 animals. Furthermore, evidence of apoptosis w as observed within 12 hours of cochlea removal, suggesting that the molecul ar events leading to cell loss after afferent deprivation begin to occur wi thin 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 sus ceptibility to removal of afferent input comparable to neonatal sensitivity of wild-type controls. These data suggest that bcl-2 is one effector of ce ll survival as these cells switch from afferent-dependent to -independent s urvival mechanisms. J. Comp. Neurol. 426:561-571, 2000. (C) 2000 Wiley-Liss , Inc.