PDF(Pubmed)
Abstract：
Vestibular hair cells (HCs) are mechanoreceptors that sense head motions by modulating the firing rate of vestibular ganglion neurons (VGNs), whose central processes project to vestibular nucleus neurons (VNNs) and cerebellar neurons. We explored vestibular function after HC destruction in adult Pou4f3+/DTR (DTR) mice, in which injections of high-dose (50 ng/g) diphtheria toxin (DT) destroyed most vestibular HCs within 2 weeks. At that time, DTR mice had lost the horizontal vestibulo-ocular reflex (aVORH), and their VNNs failed to upregulate nuclear cFos expression in response to a vestibular stimulus (centrifugation). Five months later, 21 and 14% of HCs were regenerated in utricles and horizontal ampullae, respectively. The vast majority of HCs present were type II. This degree of HC regeneration did not restore the aVORH or centrifugation-evoked cFos expression in VNNs. The failure to regain vestibular pathway function was not due to degeneration of VGNs or VNNs because normal neuron numbers were maintained after HC destruction. Furthermore, sinusoidal galvanic stimulation at the mastoid process evoked cFos protein expression in VNNs, indicating that VGNs were able to regulate VNN activity after HC loss. aVORH and cFos responses in VNNs were robust after low-dose (25 ng/g) DT, which compared to high-dose DT resulted in a similar degree of type II HC death and regeneration but spared more type I HCs in both organs. These findings demonstrate that having more type I HCs is correlated with stronger responses to vestibular stimulation and suggest that regenerating type I HCs may improve vestibular function after HC loss.
摘要：
前庭毛细胞（HCs）是通过调节前庭神经节神经元（VGN）的放电率来感知头部运动的机械感受器，其中心过程投射到前庭核神经元（VNN）和小脑神经元。我们探索了成年Pou4f3/DTR（DTR）小鼠HC破坏后的前庭功能，其中注射大剂量（50ng/g）白喉毒素（DT）在2周内破坏了大多数前庭HC。当时,DTR小鼠失去了水平前庭眼反射（aVORH），它们的VNN未能响应前庭刺激（离心）而上调核cFos表达。五个月后,21％和14％的HC在Utricle和水平壶腹中再生，分别。存在的绝大多数HC是II型。这种程度的HC再生不能恢复VNN中aVORH或离心诱发的cFos表达。未能恢复前庭通路功能不是由于VGN或VNN的变性，因为HC破坏后维持了正常的神经元数量。此外，乳突处的正弦电刺激诱发VNN中的cFos蛋白表达，表明VGN能够在HC损失后调节VNN活性。在低剂量(25ng/g)DT后，VNN中的aVORH和cfos反应是稳健的，与高剂量DT相比，这导致了相似程度的II型HC死亡和再生，但在两个器官中都保留了更多的I型HC。这些发现表明，具有更多的I型HC与对前庭刺激的更强反应相关，并表明再生I型HC可以改善HC丢失后的前庭功能。
