CELL INTERACTIONS IN THE DEVELOPING AUDITORY SYSTEM

发育中的听觉系统中的细胞相互作用

基本信息

批准号：
3215860
负责人：
THOMAS N PARKS
金额：
$ 25.24万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
1979
资助国家：
美国
起止时间：
1979-03-01 至 1993-08-31
项目状态：
已结题

项目摘要

The proposed experiments, would make use of experimental embryology, in vitro brain slices, electrophysiology, light and electron microscopy, and pharmacology, to study how interactions between functionally-linked cells or tissues contribute to development of the nervous system. One group of experiments would examine interactions between axons and their target cells during development of stereotyped patterns of synaptic connections in be brain stem auditory system of chick embryos. Early destruction of the otocyst (embryonic precursor of the inner ear and cochlear nerve) induces formation of an anomalous functional axonal projection connecting the cochlear nuclei on the two sides of the brain. Data on developmental interactions between these abnormal synaptic partners will be compared will previous work on normal development to answer the questions: 1) How does a change in the kind of afferent synaptic input affect the type of postsynaptic excitatory amino acid receptor in the cochlear nucleus? 2) Does the anomalous projection save its target neurons from deafferentation-induced neuronal death? 3) Is the number of afferent axons converging on a given target cell determined by the target or by the afferents?, 4) Is the timing and/or extent of developmental synapse elimination and reduction in afferent branching influenced by the target cells or are they properties of the afferent themselves?, and 5) Are the processes described in (4) dependent upon normal patterns of electrical activity in the afferents? A second group of experiments will use surgical manipulations of the external and middle ear rudiments of chick embryos to produce animals with a very early congenital conductive hearing loss. The effects of this deprivation on the cochlea and cochlear nucleus will be assessed electrophysiologically and morphologically, with the aim of answering two questions: 1) Is cochlear damage required to produce morphological changes in the brain stem auditory nuclei after deprivation?, and 2) Does a purely conductive hearing loss induced early in life ultimately result in early sensorineural hearing loss? It may be quite important for the success of restorative programs for be hearing-disabled to understand the neural changes accompanying early hearing loss. The proposed studies include early manipulations of the external, middle, and internal ears, with subsequent study of structure and function development in an cochlea and brain in an animal whose hearing, like man's, begins well before birth. Thus, the proposed experiments should contribute to a detailed and comprehensive understanding of be effects on auditory system development of early conductive and sensorineural hearing loss.

拟议的实验将利用实验胚胎学、体外脑切片、电生理学、光和电子显微镜和药理学，研究相互作用如何功能相连的细胞或组织之间有助于神经系统的发育。一组实验将检查轴突与其靶细胞之间的相互作用突触连接定型模式的发展鸡胚胎的脑干听觉系统。及早销毁耳囊（内耳和耳蜗的胚胎前身）神经）诱导异常功能轴突的形成连接两侧耳蜗核团的投影脑。有关这些异常之间发育相互作用的数据突触伙伴将与之前正常工作进行比较发展来回答以下问题： 1）如何改变传入突触输入的类型影响突触后的类型耳蜗核中的兴奋性氨基酸受体？ 2) 是否异常投影将其目标神经元从传入神经阻滞引起的神经元死亡？ 3）是数量传入轴突会聚在给定的目标细胞上，该目标细胞由目标或传入？, 4) 的时间和/或程度是发育性突触消除和传入神经减少分支受靶细胞影响还是它们的特性传入本身？，以及 5）（4）中描述的过程是否取决于正常的电活动模式传入？第二组实验将使用外科手术操作鸡胚的外耳和中耳雏形患有早期先天性传导性听力损失的动物。这这种剥夺对耳蜗和耳蜗核的影响将进行电生理学和形态学评估，回答两个问题的目的：1）是否需要耳蜗损伤使脑干听觉核团产生形态变化剥夺后？以及 2) 纯传导性听力损失是否会导致听力损失？生命早期诱发的最终结果是早期感音神经性听力损失？这对于恢复计划的成功可能非常重要让听力障碍者了解神经变化伴随早期听力损失。拟议的研究包括早期对外耳、中耳和内耳的操作，随后对结构和功能开发进行研究动物的耳蜗和大脑，其听觉像人类一样开始早在出生前。因此，所提出的实验应该有助于对be的详细和全面的了解早期传导和听觉系统发育的影响感音神经性听力损失。