目的:耳蜗毛细胞听神经传入突触丧失,叫做耳蜗突触病,是人类常见的病理由老化和噪音过度暴露引起的。与其他耳蜗病理分离的突触病的感知后果尚不清楚。动物模型提供了一种有效的方法来解决听觉神经丢失的生理和感知后果的不确定性。因为神经损伤可以诱导和容易量化。鹦鹉,一种鹦鹉,最近已成为突触病研究的动物模型,其基于其语音学习能力和行为区分具有类似于人类的敏锐度的简单和复杂声音的能力。虎尾草中的红藻氨酸输注会导致复合听觉神经反应的严重减少,包括听觉脑干反应的波I,不影响生理毛细胞措施。这些结果表明选择性听觉神经损伤。然而,海人酸神经损伤的组织学相关性仍然缺乏。
方法:我们量化了耳蜗内输注海藻酸(1mM;2.5µL)引起的组织学影响,并评估听神经状态的组织学和生理学评估之间的相关性。
结果:鹦鹉中的海藻酸输注导致耳蜗神经节中的神经听神经窝明显丢失(平均60%),和外周轴突,在受伤后2个月或更长时间的时间点。毛细胞上皮不受海藻酸的影响。神经丢失与复合听神经反应和听觉脑干反应波I的减少显着相关。
结论:复合听神经反应和脑干反应波I在该动物模型中提供了耳蜗突触病的有用指标。
OBJECTIVE: Loss of auditory nerve afferent synapses with cochlear hair cells, called cochlear synaptopathy, is a common pathology in humans caused by aging and noise overexposure. The perceptual consequences of synaptopathy in isolation from other cochlear pathologies are still unclear. Animal models provide an effective approach to resolve uncertainty regarding the physiological and perceptual consequences of auditory nerve loss, because neural lesions can be induced and readily quantified. The
budgerigar, a parakeet species, has recently emerged as an animal model for synaptopathy studies based on its capacity for vocal learning and ability to behaviorally discriminate simple and complex sounds with acuity similar to humans. Kainic acid infusions in the
budgerigar produce a profound reduction of compound auditory nerve responses, including wave I of the auditory brainstem response, without impacting physiological hair cell measures. These results suggest selective auditory nerve damage. However, histological correlates of neural injury from kainic acid are still lacking.
METHODS: We quantified the histological effects caused by intracochlear infusion of kainic acid (1 mM; 2.5 µL), and evaluated correlations between the histological and physiological assessments of auditory nerve status.
RESULTS: Kainic acid infusion in budgerigars produced pronounced loss of neural auditory nerve soma (60% on average) in the cochlear ganglion, and of peripheral axons, at time points 2 or more months following injury. The hair cell epithelium was unaffected by kainic acid. Neural loss was significantly correlated with reduction of compound auditory nerve responses and auditory brainstem response wave I.
CONCLUSIONS: Compound auditory nerve responses and wave I provide a useful index of cochlear synaptopathy in this animal model.