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：
3215857
负责人：
THOMAS N PARKS
金额：
$ 22.29万
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.

提出的实验将使用实验胚胎学，体外脑切片，电生理学，光和电子显微镜和药理学，以研究相互作用的方式在功能连接的细胞或组织之间有助于神经系统的发展。一组实验将检查轴突与其目标细胞之间的相互作用开发BE中突触连接的刻板印象模式小鸡胚胎的脑干听觉系统。早期破坏耳囊（内耳和人工耳蜗的胚胎前体神经）诱导异常功能轴突的形成投影连接在该耳蜗的两侧的两侧脑。这些异常之间的发展相互作用的数据将比较突触伙伴将在正常情况下进行以前的工作开发回答问题：1）一种传入突触输入会影响突触后的类型耳蜗核中的兴奋性氨基酸受体？ 2）做异常投影将其靶神经元免于脱落引起的神经元死亡？ 3）是传入轴突在给定的目标细胞上收敛目标还是传入？，4）时间和/或范围是发育突触消除和减少传入受靶细胞影响的分支，或它们是传入本身吗？和5）（4）中描述的过程是否描述取决于正常的电活动模式传入？第二组实验将使用雏鸡胚胎的外耳和中耳的基础先天性导电性听力损失的动物。这这种剥夺对耳蜗和耳蜗核的影响将在电生理和形态学上进行评估，回答两个问题的目的：1）是需要耳蜗损害在脑干听觉核中产生形态学变化剥夺之后？和2）纯粹的导电听力损失是诱发生命早期最终导致早期感觉到听力损失？这对于恢复计划的成功可能非常重要为了听取听力来了解神经变化伴随着早期听力损失。拟议的研究包括早期对外耳和内耳的操纵随后研究结构和功能发展像人类一样的听力开始的动物中的耳蜗和大脑出生前。因此，提出的实验应有助于对BE的详细而全面的理解对早期导电的听觉系统发展的影响感官听力损失。