Afferent Influences on Auditory System Ontogeny

传入对听觉系统个体发育的影响

• 批准号: 6819950
• 负责人: Edwin W Rubel
• 金额: $ 39.77万
• 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 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6819950
• 关键词: action potentials; auditory nuclei; auditory pathways; biological signal transduction; brain stem; calcium indicator; calcium transporting ATPase; cell death; chick embryo; chickens; cysteine endopeptidases; dendrites; developmental neurobiology; enzyme activity; gene deletion mutation; gene expression; genetically modified animals; glutamate receptor; laboratory mouse; microarray technology; neuroanatomy; neurogenetics; neurophysiology; neuroregulation; protein structure function; receptor coupling; sensory deprivation

DESCRIPTION (provided by applicant): Understanding normal and abnormal brain development requires knowledge of the cellular events whereby differential experience influences the ontogeny of neural structure and function. Research in this area 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 whereby the integrity and activity of the inner influences development of brainstem auditory pathways. Three separate lines of investigation are proposed: 1) We will continue to investigate the hypothesis that intracellular calcium homeostasis plays a key role in regulating the initiation of events leading to Tran neuronal cell death of brainstem neurons in the neonatal mammalian auditory pathways. Specific studies involve comparing changes in cochlear nucleus neurons following reversible inhibition of auditory nerve activity with changes produced by destruction of the inner ear, studies of calcium homeostasis in normal neurons and those deprived of excitatory input, and studies examining the role of plasma membrane ATPases in the regulation of calcium in deprived neurons. 2) The auditory system, like other sensory systems, is particularly sensitive to peripheral pathology during early development. Our second goal is to further understand the biological basis responsible for this "critical period." We will use normal and mutant mice to examine the contribution of specific genes to these changes in susceptibility. We will use micro array technology to screen for new candidate genes, and then directly assay the new gene products for their role in establishing this critical period. 2) We combine single cell labeling, electro physiology, and calcium imaging methods to study the cellular mechanisms of afferent regulation of dendritic structure. These studies make use of the unique binaural innervation of n. laminar is cells to allow spatial resolution of the relationships between afferent stimulation, calcium homeostasis, and structural dynamics of dendrites.

描述（由申请人提供）：了解正常和异常的脑发育需要了解细胞事件，从而差异经验会影响神经结构和功能的关系。这一领域的研究已经实现了新的和直接的临床重要性，随着先天和初步听力受损的婴儿的人工耳蜗的使用日益增加。该应用程序为一项研究计划寻求持续资金，旨在了解细胞事件，从而在内部影响脑干听觉途径的发展的完整性和活动。提出了三种单独的调查线： 1）我们将继续研究以下假设：细胞内钙稳态在调节导致新生儿哺乳动物听觉途径中脑干神经元的tran神经元细胞死亡的事件中起关键作用。具体的研究涉及比较可逆性抑制听觉神经活性后的耳蜗核神经元的变化与因内耳破坏而产生的变化，正常神经元中钙稳态的研究以及剥夺兴奋性输入的研究以及研究了剥离神经元中质膜膜法规的作用。 2）听觉系统与其他感觉系统一样，对早期发育期间的外围病理特别敏感。我们的第二个目标是进一步理解负责这个“关键时期”的生物学基础。我们将使用正常和突变小鼠检查特定基因对这些易感性变化的贡献。我们将使用微阵列技术来筛选新的候选基因，然后直接分析新基因产品，以在建立这个关键时期中的作用。 2）我们结合了单个细胞标记，电生理和钙成像方法，以研究树突结构传入调节的细胞机制。这些研究利用了n的独特双耳神经。层流是可以使传入刺激，钙稳态和树突的结构动力学之间的关系空间分辨的细胞。