ANIMAL NEUROANATOMY

动物神经解剖学

• 批准号: 6234269
• 负责人: DOROTHY G FLOOD
• 金额: $ 2万
• 依托单位: ROCHESTER INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-06-15 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6234269
• 关键词: afferent nerve; aging; auditory nuclei; axon; cochlea; dendrites; disease /disorder model; ear hair cell; efferent nerve; electron microscopy; genetic strain; horseradish peroxidase; immunocytochemistry; inferior colliculus; injection /infusion; laboratory mouse; laboratory rat; light microscopy; neural information processing; neuroanatomy; neurotransmitters; olivary body; presbycusis; silver impregnation; soma; sound frequency; synapses; tissue /cell culture

The neuroanatomical basis of presbycusis in the central auditory system has not been extensively studied, nor has it been extensively related to neurophysiological findings. Because presbycusis is a human problem, it would be desirable to study its morphological basis in humans. However, morphological study of humans that have had their premortem auditory function well-characterized behaviorally and/or physiologically is extremely difficult. Thus, animal models of certain aspects of presbycusis, the CBA/J and C57BL/6J strains of mice, have been chosen. The CBA/J strain undergoes presbycusis changes late in its life, like the human, but over the full frequency range. The C57BL/6J strain shows hearing losses early in life that progress rapidly in severity. The losses begin at high frequencies and progress towards lower frequencies, as in the human. This study will examine neuroanatomical changes in aging with and without hearing loss in mice that have been tested for auditory function behaviorally (acoustic startle reflex) and physiologically (auditory nerve responses and auditory brainstem responses). In order to evaluate the age- related changes in the morphology of the peripheral auditory system, we will determine the amount of hair cell loss and strial atrophy in the cochleas of the two strains of mice and in rats of Project 2. We will study morphological changes in the central nucleus of the inferior colliculus (ICC). It is:1) a region in which frequency and temporal processing of sounds will be investigated physiologically in Project 3,2) the region in which most information from lower brainstem centers collects before being transmitted to thalamus and cortex, and 3) a region in which changes have been reported in aging rodents. Mice of the following ages and strains will be utilized: 1-2, 6-8, and >24 mos for the CBA/J strain and 1-2, 6-8, and 30-32 mos for the C57BL/6J strain. Morphological studies of the ICC in aging with and without hearing loss fall into three categories: 1) integrity, 2) changes in connectivity, and 3) changes in the morphology of inhibitory neurotransmitter systems. All morphological studies will subdivide the ICC based upon its tonotopic organization into high and low frequency regions. Integrity of the ICC will be determined by measuring numbers and sizes of neurons and the volume of the ICC at the light microscopic level, and by describing changes in neuronal morphology at the electron microscopic level. HRP-injected mice, studied in Project 3 with single-unit physiological techniques, will be used to map physiological functions to anatomical locations in the ICC. Connectivity of the ICC will be determined by quantifying dendritic extent in Golgi- impregnated material, and quantifying synaptic numbers and sizes in electron microscopic material. The numbers and sizes of afferent cell bodies and numbers of efferent terminals, visualized with HRP injections of the ICC, will be quantified. Also in the C57BL/6J mice, reorientation of dendritic trees and reorganization of HRP-filled afferents will be studied to identify the morphological basis of the age-related tonotopic reorganization of the ICC. Morphological correlates of inhibitory function in the ICC will be studied immunohistochemically in material stained for the neurotransmitter systems of GABA and glycin. Numbers of immunohistochemically stained terminals and cell bodies and sizes of cell bodies will be quantified. Additionally, a limited number of morphological studies will be performed in the superior olivary complex (SCC) one of the major inputs to the ICC. These studies will include the measurement of numbers and sizes of neurons in Nissi-stained material and in immunohistochemically stained material, as a function of the morphologically identifiable subnuclei of the SOC.

中枢听觉系统老年性耳聋的神经解剖学基础 没有被广泛研究，也没有广泛相关 神经生理学发现。 因为老年性耳聋是一个人类问题， 研究其在人类中的形态学基础是可取的。 然而， 对死前听觉人类的形态学研究 行为和/或生理上明确表征的功能是 极其困难。 因此，某些方面的动物模型 选择了老年性耳聋小鼠的 CBA/J 和 C57BL/6J 品系。 这 CBA/J 菌株在其生命后期会经历老年性耳聋变化，就像 人类，但在整个频率范围内。 C57BL/6J 菌株显示 生命早期的听力损失，严重程度迅速恶化。 损失 从高频开始，逐渐向低频发展，如 人类。 这项研究将检查衰老过程中的神经解剖学变化 经过听觉功能测试的小鼠没有听力损失 行为上（听觉惊吓反射）和生理上（听觉神经） 反应和听觉脑干反应）。 为了评估年龄—— 周围听觉系统形态的相关变化，我们 将确定毛细胞损失和纹状体萎缩的数量 两种小鼠品系和项目 2 的大鼠的耳蜗。我们将 研究下中央核的形态变化 丘（ICC）。 它是：1）频率和时间的区域 声音的处理将在项目 3,2) 中进行生理学研究 下脑干中心收集大部分信息的区域 在传输到丘脑和皮质之前，以及 3) 一个区域 据报道，衰老的啮齿动物发生了变化。 以下年龄段的小鼠 将使用的菌株：CBA/J 菌株为 1-2、6-8 和 >24 mos C57BL/6J 菌株为 1-2、6-8 和 30-32 mos。 形态学研究 ICC 在有听力损失和无听力损失的情况下的衰老分为三类 类别：1）完整性，2）连通性变化，3） 抑制性神经递质系统的形态。 所有形态 研究将根据 ICC 的基调组织将 ICC 细分为 高频区和低频区。 国际刑事法院的完整性将由以下因素决定： 测量神经元的数量和大小以及 ICC 的体积 光显微镜水平，并通过描述神经元形态的变化 在电子显微镜水平上。 注射 HRP 的小鼠，在项目中进行研究 3 具有单单元生理学技术，将用于绘制图 ICC 中解剖位置的生理功能。 连接性 ICC 的大小将通过量化高尔基体中的树突程度来确定 浸渍材料，并量化突触数量和大小 电子显微材料。 传入细胞的数量和大小 身体和传出终端的数量，通过 HRP 注射可视化 ICC将被量化。 同样在 C57BL/6J 小鼠中， 将研究树突树和 HRP 填充传入神经的重组 确定与年龄相关的音位的形态学基础 国际刑事法院的重组。 抑制功能的形态学相关性 将在 ICC 中对染色材料进行免疫组织化学研究 GABA 和甘氨酸的神经递质系统。 数量 免疫组织化学染色的末端和细胞体以及细胞大小 身体将被量化。 此外，数量有限的形态 研究将在上橄榄复合体（SCC）中进行，其中之一是 对国际刑事法院的主要投入。 这些研究将包括测量 尼西染色材料中神经元的数量和大小以及 免疫组织化学染色材料，作为 SOC 形态上可识别的亚核。