SYNAPTIC CORRELATES OF ACQUIRED AND HERITABLE DEAFNESS

获得性和遗传性耳聋的突触相关性

• 批准号: 6238191
• 负责人: John K. Niparko
• 金额: $ 10.16万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6238191
• 关键词: animal age group; auditory nuclei; auditory pathways; cats; cochlear implants; congenital deafness; developmental neurobiology; disease /disorder model; electron microscopy; electrophysiology; genetic disorder; morphology; neuroanatomy; neurons; synapses; tetrodotoxin

Our long term goal is to understand the mechanisms that account for the influence of neural activity on synaptic morphology. Neurons of the central auditory pathway and their synaptic connections undergo considerable change as a consequence of deafness, possibly under the direct influence of spike activity in the auditory nerve. Two models of deafness will be investigated in order to study this phenomenon: One model is the acutely deafened cat whose condition can be experimentally-induced- via chemical treatment. The other model is the congenitally deaf white cat, where we know that there is a naturally-occurring progressive loss of sensory receptors with age that begins shortly after birth. This model mimics a heritable hearing disorder found in humans. Significant morphologic changes at the synaptic interface between auditory nerve fibers and cochlear nucleus neurons are observable in both models of deafness. The present proposal seeks to use electrophysiologic and anatomic techniques to examine the role of acute versus chronic hearing loss on the structural integrity of the central auditory system. We will test the hypothesis that auditory nerve activity is an important presynaptic determinant for normal ending structure and postsynaptic neuronal form in the cochlear nucleus. The impact of presynaptic factors on the central auditory pathway across developmental stages will also be studied. Identification of presynaptic variables that affect the central auditory pathway will bear a direct relevance to the processing capabilities of prosthetically restored input. Correlation of the time of onset and form of deafness with these variables may be important in guiding the future selection of promising implant patients.

我们的长期目标是了解解释这一现象的机制 神经活动对突触形态的影响。的神经元 中枢听觉通路及其突触连接经历 耳聋可能造成相当大的变化 听觉神经尖峰活动的直接影响。两种型号 为了研究这一现象，我们将对耳聋进行调查：一个模型 是一只严重耳聋的猫，其病症可以通过实验诱发—— 通过化学处理。另一种型号是先天性聋哑白人 猫，我们知道存在自然发生的渐进性丧失 感觉受体随着年龄的增长在出生后不久就开始出现。这个型号 模仿人类发现的遗传性听力障碍。重要的 听神经突触界面的形态变化 在两种模型中都可以观察到纤维和耳蜗核神经元 耳聋。 目前的提案旨在利用电生理学和解剖学 检查急性与慢性听力损失对听力损失的影响的技术 中枢听觉系统的结构完整性。我们将测试 假设听觉神经活动是重要的突触前神经活动 正常末端结构和突触后神经元形式的决定因素 耳蜗核。突触前因素对中枢的影响 还将研究跨发育阶段的听觉通路。 识别影响中枢听觉的突触前变量 路径将与处理能力直接相关 修复性恢复输入。发病时间与形式的相关性 对这些变量的耳聋可能对指导未来很重要 选择有前途的种植患者。