Department of Biomedical Engineering, University of Rochester, Rochester, NY 14642, USA.
Department of Neuroscience, University of Rochester, Rochester, NY 14642, USA.
J Assoc Res Otolaryngol. 2023 Oct;24(5):473-485. doi: 10.1007/s10162-023-00910-5. Epub 2023 Oct 5.
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.
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.
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.
Compound auditory nerve responses and wave I provide a useful index of cochlear synaptopathy in this animal model.
与耳蜗毛细胞失去听觉神经传入突触，称为耳蜗突触病，是一种常见的病理学，由衰老和噪声过度暴露引起。突触病在与其他耳蜗病变分离的情况下的感知后果仍然不清楚。动物模型提供了一种有效的方法来解决关于听觉神经损失的生理和感知后果的不确定性，因为可以诱导神经病变并容易量化。虎皮鹦鹉，一种长尾鹦鹉物种，由于其发声学习的能力以及能够以类似于人类的敏锐度行为区分简单和复杂的声音，最近成为突触病研究的动物模型。在虎皮鹦鹉中，红藻氨酸的输注会导致复合听觉神经反应（包括听觉脑干反应的 I 波）的显著减少，而不会影响生理毛细胞的测量。这些结果表明存在选择性听觉神经损伤。然而，红藻氨酸引起的神经损伤的组织学相关性仍然缺乏。
我们量化了红藻氨酸（1mM；2.5µL）内耳蜗内输注引起的组织学效应，并评估了听觉神经状态的组织学和生理学评估之间的相关性。
红藻氨酸输注在虎皮鹦鹉的耳蜗神经节中产生了明显的神经听觉神经体（平均 60%）丧失，以及外周轴突的丧失，在损伤后 2 个月或更长时间点。毛细胞上皮不受红藻氨酸的影响。神经损失与复合听觉神经反应和听觉脑干反应 I 波的减少显著相关。
复合听觉神经反应和 I 波为该动物模型中的耳蜗突触病提供了有用的指标。
