Goode C T, Carey J P, Fuchs A F, Rubel E W
Program in Neurobiology and Behavior, University of Washington, Seattle, Washington 98195, USA.
J Neurophysiol. 1999 Mar;81(3):1025-35. doi: 10.1152/jn.1999.81.3.1025.
Avian auditory and vestibular hair cells regenerate after damage by ototoxic drugs, but until recently there was little evidence that regenerated vestibular hair cells function normally. In an earlier study we showed that the vestibuloocular reflex (VOR) is eliminated with aminoglycoside antibiotic treatment and recovers as hair cells regenerate. The VOR, which stabilizes the eye in the head, is an open-loop system that is thought to depend largely on regularly firing afferents. Recovery of the VOR is highly correlated with the regeneration of type I hair cells. In contrast, the vestibulocolic reflex (VCR), which stabilizes the head in space, is a closed-loop, negative-feedback system that seems to depend more on irregularly firing afferent input and is thought to be subserved by different circuitry than the VOR. We examined whether this different reflex also of vestibular origin would show similar recovery after hair cell regeneration. Lesions of the vestibular hair cells of 10-day-old chicks were created by a 5-day course of streptomycin sulfate. One day after completion of streptomycin treatment there was no measurable VCR gain, and total hair cell density was approximately 35% of that in untreated, age-matched controls. At 2 wk postlesion there was significant recovery of the VCR; at this time two subjects showed VCR gains within the range of control chicks. At 3 wk postlesion all subjects showed VCR gains and phase shifts within the normal range. These data show that the VCR recovers before the VOR. Unlike VOR gain, recovering VCR gain correlates equally well with the density of regenerating type I and type II vestibular hair cells, except at high frequencies. Several factors other than hair cell regeneration, such as length of stereocilia, reafferentation of hair cells, and compensation involving central neural pathways, may be involved in behavioral recovery. Our data suggest that one or more of these factors differentially affect the recovery of these two vestibular reflexes.
鸟类的听觉和前庭毛细胞在受到耳毒性药物损伤后能够再生，但直到最近，几乎没有证据表明再生的前庭毛细胞能正常发挥功能。在早期的一项研究中，我们发现氨基糖苷类抗生素治疗会消除前庭眼反射（VOR），而随着毛细胞再生，该反射会恢复。VOR能使眼球在头部保持稳定，是一个开环系统，一般认为它很大程度上依赖于规律发放冲动的传入神经。VOR的恢复与I型毛细胞的再生高度相关。相比之下，前庭脊髓反射（VCR）能使头部在空间中保持稳定，是一个闭环负反馈系统，似乎更多地依赖于不规则发放冲动的传入神经输入，并且一般认为它由与VOR不同的神经回路介导。我们研究了这种同样起源于前庭的不同反射在毛细胞再生后是否也会表现出类似的恢复情况。通过为期5天的硫酸链霉素处理，造成10日龄雏鸡前庭毛细胞损伤。链霉素治疗结束后1天，未检测到VCR增益，此时总的毛细胞密度约为未处理的、年龄匹配的对照组的35%。损伤后2周，VCR有显著恢复；此时有两个实验对象的VCR增益处于对照雏鸡的范围内。损伤后3周，所有实验对象的VCR增益和相位偏移均在正常范围内。这些数据表明，VCR比VOR恢复得早。与VOR增益不同，恢复中的VCR增益与再生的I型和II型前庭毛细胞的密度同样密切相关，但在高频时除外。除了毛细胞再生外，还有其他几个因素可能参与行为恢复，如静纤毛的长度、毛细胞的再传入以及涉及中枢神经通路的代偿。我们的数据表明，这些因素中的一个或多个对这两种前庭反射的恢复有不同的影响。
