ANIMAL NEUROANATOMY

动物神经解剖学

• 批准号: 3726559
• 负责人: DOROTHY G FLOOD
• 金额: --
• 依托单位: ROCHESTER INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3726559
• 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有 没有得到广泛的研究，也没有广泛地与 神经生理学发现。因为老年性耳聋是人类的问题，所以它 在人类身上研究它的形态基础是可取的。然而， 对死前有听觉障碍的人类的形态研究 行为和/或生理特征良好的功能是 非常困难。因此，某些方面的动物模型 选用CBA/J和C57BL/6J两个品系的小鼠老年性耳聋。这个 CBA/J株在其生命的后期经历了老年性耳聋的变化，如 人类，但在整个频率范围内。C57BL/6J菌株显示 听力损失在生命的早期，严重程度迅速增加。损失惨重 从高频开始，向低频率发展，如在 人类。这项研究将研究衰老过程中神经解剖学的变化。 在接受了听觉功能测试的小鼠中没有听力损失 行为(听觉惊吓反射)和生理(听神经) 反应和听觉脑干反应)。为了评估年龄- 外周听觉系统形态的相关变化，我们 将决定毛细胞脱落量和眼球萎缩程度 两个品系的小鼠和项目2的大鼠的耳蜗。我们将 下丘脑中央核形态变化的研究 丘脑(ICC)。它是：1)频率和时间 在项目3，2中将对声音的处理进行生理学研究 来自低级脑干中心的大多数信息收集的区域 在被传递到丘脑和皮质之前，以及3)其中 据报道，在老化的啮齿动物中发生了变化。以下年龄的小鼠 将使用的菌株：CBA/J株为1-2、6-8和&gt；24mos C57BL/6J株为1-2、6-8和30-32mos。形态研究 老年伴和不伴听力损失的ICC分为三组 类别：1)完整性，2)连通性变化，以及3) 抑制性神经递质系统的形态。所有形态 研究将根据ICC的主题组织将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 测量神经细胞的数量、大小和ICC的体积 光镜水平，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，项目研究 3用单单位生理学技术，将被用来映射 生理功能在ICC内的解剖位置。连通性 ICC的数量将通过量化高尔基体中的树枝状程度来确定- 浸渍材料，并量化突触的数量和大小 电子显微镜材料。传入细胞的数量和大小 HRP注射显示的传出末梢的小体和数目 国际刑事法院，将被量化。同样在C57BL/6J小鼠中，重定向 将研究树状结构树和HRP填充的传入神经的重组 确定与年龄相关的直视的形态学基础 国际刑事法院的重组。抑制功能的形态相关 在ICC中将被免疫组织化学染色的材料进行研究 GABA和甘氨酸的神经递质系统。数量 免疫组织化学染色的终末和胞体及细胞大小 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 对国际刑事法院的主要投入。这些研究将包括测量 尼氏染色材料中神经元的数量和大小 免疫组织化学染色的物质，作为 在形态上可识别的SOC亚核。