POSTNATAL DEVELOPMENT OF OLIVOCOCHLEAR NEURONS

描述：负责成年人的个体发育机制 哺乳动物耳蜗内的神经支配和功能模式是 不太了解。此应用程序的目标是调查 传出突触发生的基础机制，特别是， 橄榄耳蜗（OC）突触的发育。另一个目标是测试 目前突触发生和竞争模型的普遍性， OC系统的成熟，以及最终的听觉功能。以来 OC神经元表现出最好的频率响应，参与了 在噪声中检测信号，并出现形态成熟之前， 听力的开始，了解他们的发展可能有助于我们 了解早产儿的听力和与听力相关的疾病， 新生儿具体目的是检验以下假设： 1)内侧OC神经元表现出发育等待期，也就是说，它们 将投射发送到耳蜗，在中间目标上形成突触，2） 内侧OC神经元能够释放乙酰胆碱之前， 外毛细胞上的突触，和3）外侧OC神经元经历 耳蜗突触发生与内侧OC神经元的分离期。这些 调查主要集中在新生儿出生后第一周， 仓鼠和沙鼠，包括各种方法，如： 逆行和顺行标记，以显示 传出投射以及传出神经元的突触输入; 标记的传出终末的连续切片电子显微镜; 组织化学、免疫化学和原位杂交研究 神经递质和发育标志物的表达;以及 表征酶活性以评估神经递质机制。 重要的是，这项研究应该产生特定的模型， 通过实验干预进行测试。

DESCRIPTION: 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 olivocochlear (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 to understand hearing and disorders associated with hearing in preterm and newborn infants. The specific aims are to test the following hypothesis: 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, and 3) lateral OC neurons undergo a separate period of cochlear synaptogenesis from medial OC neurons. 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 as well as synaptic input to the efferent neurons; serial-section electron microscopy of labeled efferent terminals; histochemical, immunochemical, and in situ hybridization studies of the expression of neurotransmitters and developmental markers; and characterization of enzyme activity to assess neurotransmitter mechanisms. Importantly, this research should generate specific models that can be tested by experimental interventions.