DEVELOPMENT OF EFFERENT NERVE FIBERS IN THE COCHLEA

耳蜗传出神经纤维的发育

• 批准号: 3217056
• 负责人: HANNA M SOBKOWICZ
• 金额: $ 19.13万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3217056
• 关键词: acetylcholine; calcitonin; cell differentiation; choline acetyltransferase; cholinesterase inhibitors; cochlea; ear hair cell; efferent nerve; electron microscopy; enkephalins; histochemistry /cytochemistry; immunochemistry; infant animal; laboratory mouse; methionine; microscopy; monoclonal antibody; neuroanatomy; neurochemistry; neurofilament; neurogenesis; neuropeptides; neurotransmitter metabolism; organ of Corti; parasympathetic nervous system; synapses

Fundamental to the acquisition of communication skills is the normal development of hearing. At the neural level, the development of hearing requires the proper development of the sensory receptor cells in the inner ear (inner and outer hair cells) and their innervation by afferent and efferent fibers. Presently, the molecular and morphological processes that lead to the differentiation of this neural system are poorly understood. Thus, we propose to initiate a series of investigation to begin to understand those processes. The goal of this research is to comprehend the molecular and morphological development of the efferent innervation in the organ of Corti of the mouse. Recent studies suggest that the efferent system may consist of discrete neuronal subunits that differ functionally depending on heir biochemical characteristics. We propose, therefore, to use biochemical, histochemical and immunocytochemical techniques to study the expression of the enzymes of acetylcholine metabolism - choline acetyltransferase (ChAT), AchE and the molecular forms of AChE - and the neuropeptide neurotransmitters methionine-enkepalin and calcitonin gene-related pepteide in relation to the ultrastructural development of efferent fibers in the cochlea. Our data suggests that biochemical expression of the efferent fibers preceed their morphological differentiation. Thus, we expect these techniques to provide a sensitive probe for the early detection of efferent fibers to study the patterns of their growth and differentiation. Futhermore, our evidence of the molecular diversity of the cholinergic system along the cochlear spire suggest functional differences in their synaptic apparatus. The data stress a need for selective immunological visualization to distinguish the molecular neuronal subsystems. We expect that by the means of monoclonal antibodies to different AChE molecular forms (globular 6/4S, 10S and asymmetric 16S) we will be able to determine the developmental time and the topography of different subsystems during the morphological differentiation of the efferent system.

获得沟通技巧的基础是 听觉的正常发展。 在神经层面， 发展听力需要适当的发展 内耳的感觉感受器细胞（内毛细胞和外毛细胞） 以及它们由传入和传出纤维支配的神经。 目前， 分子和形态学的过程，导致 这种神经系统的分化知之甚少。 因此，在本发明中， 我们建议启动一系列调查，开始， 理解这些过程。 这项研究的目的是了解分子和 传出神经支配的形态发育 小鼠的Corti器官。 最近的研究表明， 传出系统可以由离散的神经元亚单位组成， 根据其生化特性而在功能上不同。 因此，我们建议使用生物化学、组织化学和 免疫细胞化学技术研究的表达， 乙酰胆碱代谢酶-胆碱乙酰转移酶 （ChAT），乙酰胆碱酯酶和乙酰胆碱酯酶的分子形式-和 神经肽神经递质甲硫氨酸-恩可帕林和 降钙素基因相关肽与心肌细胞超微结构的关系 耳蜗传出纤维的发育。 我们的数据表明 传出纤维的生化表达先于它们的 形态分化 因此，我们希望这些技术 为传出神经的早期检测提供了一种敏感的探针， 纤维，以研究其生长和分化的模式。 因此，我们对这些基因的分子多样性的证据 沿着耳蜗尖沿着的胆碱能系统表明 它们的突触装置存在差异。 数据强调， 选择性免疫可视化以区分 神经元子系统 我们希望通过单克隆方法， 针对不同AChE分子形式（球状6/4S、10 S 16 S），我们将能够确定 不同子系统的发育时间和地形 在传出系统的形态分化过程中。