CELLULAR PROCESSES OF CENTRAL AUDITORY NEURONAL DEATH

描述：(改编自《调查者摘要》)内耳损伤 可由多种原因引起，包括疾病、噪音和耳毒性 毒品。对耳蜗长时间的损害可能会有持久的，往往是有害的 对中枢听觉神经元的影响，因为这些神经元依赖于连续的 正常功能的传入输入。外围设备之间的相互作用；以及 中枢神经系统在鸟类的听觉系统中得到了广泛的研究。听觉 耳蜗核(N.Magnoellaris，NM)中的神经元接受唯一的 通过第八神经从耳蜗处传入的兴奋性神经。毁掉 雏鸡的耳蜗会启动一系列快速新陈代谢 突触后NM神经元的变化，包括氧化上调 功能。在几天内，30%的NM神经元将死亡，其余的 表现出代谢活动的长期下降。当耳蜗骨受损时 在成年鸡中，NM反应的程度因品种不同而不同 动物。 在哺乳动物中，耳蜗的损伤是永久性的。然而，鸟类拥有 具有卓越的替代受损耳蜗毛细胞的能力。修复开始 在受伤的几天内，S和解剖恢复了随后的回归 有很强的听觉功能。虽然耳蜗术后恢复的机制 已经被广泛研究过了，关于中枢神经系统是如何反应的知之甚少 毛细胞的丢失和再生。在孵化的鸟类中，我们将研究NM如何 神经元对庆大霉素引起的可逆性耳蜗功能丧失做出反应。 我们将评估庆大霉素后NM神经元数量的变化 并确定是否存在可逆的氧化 就会发生上调。我们将确定NM是否产生新的神经元 类似于耳蜗毛细胞的置换。我们将在成年鸟类身上进行测试 不同中枢神经系统的基础是耳蜗功能差异的假说 不同品种鸟类对人工耳蜗术的反应。我们将评估 成年禽鸟对环境噪音的反应是否不同；以及 中枢神经系统反应是否可以通过耳蜗性完整性来预测。最后，我们会 评价成年鸟类毛细胞再生能力。 我们修复耳蜗损伤的能力正在不断提高， 人工耳蜗术的进展及人工耳蜗术后再生的可能性 哺乳动物的耳蜗毛细胞。外周修复方面的这些进步使它成为一切 评估听觉中枢神经系统的功能能力越重要。

DESCRIPTION: (Adapted from the Investigator's Abstract) Damage to the inner ear can occur from a variety of causes, including diseases, noise and ototoxic drugs. Prolonged damage to the cochlea can have lasting and often detrimental effects on auditory neurons in the CNS because these neurons rely on continuous afferent input for normal function. Interactions between the periphery; and the CNS have been studied extensively in the avian auditory system. Auditory neurons in the cochlear nucleus (n. magnocellularis, NM) receive their only excitatory input from the cochlea via the eighth nerve. Destruction of the cochlea in hatchling chickens sets in motion a series of rapid metabolic changes in postsynaptic NM neurons, including upregulation of oxidative function. Within several days, 30% of NM neurons will die and the remainder show long-lasting decreases in metabolic activity. When the cochlea is damaged in an adult chicken, the extent of the response in NM varies with the breed of animal. In mammals damage to the cochlea is permanent. However, birds have the remarkable capacity to replace damaged cochlear hair cells. Repair begins within several days of damage, and anatomical recovery s followed by the return of substantial auditory function. Although the mechanisms of cochlear recovery have been examined extensively, much less is known about how the CNS responds to hair cells loss and regeneration. In hatchling birds we will examine how NM neurons respond to reversible loss of cochlear function caused by gentamicin. We will evaluate how the number of NM neurons changes following gentamicin damage to the cochlea, and determine whether a reversible oxidative upregulation occurs. We will determine whether new neurons are generated in NM similar to the replacement of cochlear hair cells. In adult birds we will test the hypothesis that differences in cochlear function underlie the different CNS responses to cochlear ablation in birds of different breeds. We will evaluate whether adult birds differ in their response to environmental noise, and whether CNS responses can be predicted by cochlear integrity. Finally, we will evaluate the capacity for hair cell regeneration in adult birds. Our ability to repair damage to the cochlea is continuously improving, with advances in cochlear implant technology and the possibility for regeneration of mammalian cochlear hair cells. These advances in peripheral repair make it all the more crucial to assess the functional capacity of the auditory CNS.