POSTNATAL DEVELOPMENT OF OLIVOCOCHLEAR NEURONS

橄榄耳蜗神经元的产后发育

• 批准号: 2828562
• 负责人: DWAYNE D SIMMONS
• 金额: $ 3.64万
• 依托单位: CENTRAL INSTITUTE FOR THE DEAF
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-01-01 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2828562
• 关键词: acetylcholine; acetylcholinesterase; agrin; apoptosis; choline acetyltransferase; cochlea; developmental neurobiology; ear hair cell; efferent nerve; fibroblast growth factor; gamma aminobutyrate; gerbil /jird; growth factor receptors; hamsters; inferior colliculus; innervation; neural growth associated protein; neural transmission; neuromuscular junction; neuronal transport; neurons; newborn animals; olivocochlear bundle; synapsins; synaptogenesis

The ontogenetic mechanisms that are responsible for the adult patterns of innervation and function within the mammalian cochlea are poorly understood. The goal of this application is to investigate the mechanisms which underlie efferent synaptogenesis, specifically, the development of olivocochiear (OC) synapses. An additional goal is to test the generality of current models of synaptogenesis and competition in the maturation of the OC system, and ultimately, of auditory function. Since OC neurons demonstrate best frequency responses, are involved with the detection of signals in noise, and appear morphologically mature before the onset of hearing, understanding their development may help us understand hearing and disorders associated with hearing in preterm and newborn infants. The specific aims are to test the following hypotheses: 1) medial OC neurons exhibit a developmental waiting period, that is, they send projections to the cochlea that synapse on intermediate targets, 2) medial OC neurons are capable of releasing acetylcholine prior to synapsing on outer hair cells, 3) lateral OC neurons undergo a separate period of cochlear synaptogenesis from medial OC neurons, and 4) OC neurons are capable of electrical activity at the time of synapse formation. These investigations focus primarily on the first postnatal week in newborn hamsters and gerbils and include a variety of approaches such as: retrograde and anterograde labeling to visualize the temporal sequence of efferent projections; serial-section electron microscopy of labeled efferent terminals; histochemical, immunochemical, and in situ hybridization studies of the expression of neurotransmitters and developmental markers; characterization of enzyme activity to assess neurotransmitter mechanisms; and development of a brainstem slice preparation to explore the onset of activity and synaptic input to OC neurons. Importantly, this research should generate specific models that can be tested by experimental interventions. This ISA will significantly enhance the PI's development as an independent scientist by providing the much needed time to focus and direct his research, and by allowing the PI to develop and apply multidisciplinary approaches such as neurochemical, molecular, and slice physiological techniques. The institution's development plans include: 1) releasing the PI from nonessential teaching and administrative responsibilities, 2) encouraging additional mentoring between the PI and senior faculty within the department, and 3) allowing the PI to pursue research collaborations offcampus that will strengthen his research program.

负责成人模式的个体发育机制 哺乳动物耳蜗内的神经和功能很差 理解。该应用的目的是研究机制 这是传出突触发生的基础，特别是 橄榄石（OC）突触。另一个目标是测试一般性 当前的突触发生模型和竞争成熟 OC系统，最终是听觉功能。自OC神经元以来 证明最佳频率响应与检测有关 噪音中的信号，并在形态学上显得成熟 听力，了解他们的发展可能会帮助我们了解听力 以及与早产和新生婴儿听力有关的疾病。这 具体目的是检验以下假设：1）内侧OC神经元 展示了一个发育等待期，也就是说，他们发送预测 到中间靶标突触的耳蜗，2）内侧OC神经元 能够在外发突触之前释放乙酰胆碱 细胞，3）外侧OC神经元经历了单独的耳蜗期 内侧OC神经元的突触发生，4）OC神经元能够 突触形成时的电活动。这些 调查主要集中于新生儿的第一个后周 仓鼠和沙鼠，包括多种方法，例如： 逆行和顺行标记以可视化时间序列 传出预测；标记的串行部分电子显微镜 传出终端；组织化学，免疫化学和原位 神经递质和 发展标记；酶活性的表征 神经递质机制；和脑干切片的发展 准备探索活动和突触输入的OC的发作 神经元。重要的是，这项研究应生成特定模型 可以通过实验干预措施进行测试。 ISA将大大增强PI的发展 独立科学家提供非常需要的时间来集中精力和 指导他的研究，并允许PI开发和应用 多学科的方法，例如神经化学，分子和切片 生理技术。该机构的发展计划包括： 1）从非必要的教学和行政上释放PI 责任，2）鼓励PI和 部门内的高级教师，3）允许PI追求 研究合作将加强他的研究 程序。