AFFERENT INFLUENCES ON AUDITORY SYSTEM ONTOGENY

传入对听觉系统个体发育的影响

• 批准号: 6634491
• 负责人: Edwin W Rubel
• 金额: $ 41.37万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6634491
• 关键词: age difference; auditory deprivation; auditory pathways; brain stem; calcium flux; calcium indicator; cell death; chickens; cochlea; dendrites; developmental neurobiology; electrophysiology; electrostimulus; green fluorescent proteins; laboratory mouse; labyrinth; neural degeneration; neural information processing; potassium channel; tissue /cell culture; transfection

Understanding the fundamental principles of normal and abnormal brain development requires knowledge of the cellular events whereby differential experience influences the ontogeny of neural structure and function. In the auditory system, this area of research has achieved new and immediate clinical importance with the increasing use of cochlear implants in congenitally and prelingually hearing impaired infants. This application seeks continued funding for a research program aimed at understanding the cellular events underlying the influence of inner ear integrity and activity on development of brainstem auditory pathways. Four separate lines of investigation will be either continued or initiated. 1. We will continue to investigate the hypothesis that intracellular calcium homeostasis plays a key role in regulating the initiation of events leading to transneuronal cell death of brainstem neurons in young animals following damage to the inner ear or deprivation of acoustically driven inner ear activity. 2. We will investigate activity-dependent regulation of a specific molecule, a potassium channel (Kv1.1), thought to play a uniquely important role in the temporal coding of auditory information. Afferent regulation of the expression of this molecule will be examined at the levels of gene transcription, protein, and functional properties of cochlear nucleus cells. 3. We will use normal and mutant mice to examine the biological principles underlying differential susceptibility of the developing and mature brains to deprivation-induced degeneration. 4. We will combine single cell labeling, electrophysiology and calcium imaging methods to study the cellular mechanisms of afferent regulation of dendritic structure.

要了解正常和异常大脑发育的基本原理，需要了解细胞事件的知识，通过细胞事件，差异经验影响神经结构和功能的个体发育。在听觉系统方面，随着人工耳蜗术在先天和语前听力障碍婴儿中的使用越来越多，这一领域的研究已经获得了新的和直接的临床重要性。这项申请寻求继续为一项旨在了解内耳完整性和活动对脑干听觉通路发育影响的细胞事件的研究计划提供资金。将继续或启动四条不同的调查路线。1.我们将继续研究这一假说，即细胞内钙稳态在调节幼年动物内耳受损或丧失声驱动内耳活动后导致脑干神经元跨神经元死亡的事件的启动中起关键作用。2.我们将研究一种特定分子--钾通道(Kv1.1)的活性依赖性调节，该通道被认为在听觉信息的时间编码中发挥着独特的重要作用。该分子表达的传入调节将在基因转录、蛋白质和耳蜗核细胞功能特性的水平上进行研究。3.我们将使用正常小鼠和突变小鼠来研究发育中和成熟的大脑对剥夺诱导的退化的不同易感性背后的生物学原理。4.我们将结合单细胞标记、电生理学和钙离子成像等方法，研究树突状结构传入调控的细胞机制。