ANIMAL NEUROANATOMY

老年性聋的中枢听觉系统神经解剖学基础 没有被广泛研究，也没有被广泛地与 神经生理学发现。 因为老年性耳聋是人类的问题， 研究其在人类中的形态学基础将是合乎需要的。 然而，在这方面， 对人类的形态学研究， 在行为上和/或生理上充分表征的功能是 非常困难。 因此，某些方面的动物模型， 选择CBA/J和C57 BL/6 J品系的老年性耳聋小鼠。 的 CBA/J菌株在其生命后期经历老年性耳聋变化，如 人，但在整个频率范围内。 C57 BL/6 J菌株显示 听力损失在生命早期迅速发展的严重程度。 的损失 开始于高频，并向低频发展，如 人类 这项研究将探讨神经解剖学的变化， 没有听力损失的老鼠， 行为上（听觉惊吓反射）和生理上（听觉神经 听觉脑干反应（auditory brainstem response）。 为了评估年龄- 周围听觉系统形态学的相关变化，我们 将决定毛细胞损失和毛囊萎缩的数量， 两种小鼠品系和项目2大鼠的耳蜗。 我们将 观察下丘脑中央核的形态学变化 丘（ICC）。 它是：1）频率和时间的区域 声音的处理将在项目3中进行生理学研究，2） 从低位脑干中心收集信息的区域 在被传递到丘脑和皮层之前，以及3）一个区域， 在老年啮齿类动物中已经报道了变化。 以下年龄的小鼠 将使用的菌株：CBA/J菌株为1-2、6-8和>24个月 C57 BL/6 J株为1-2、6-8和30-32个月。 形态学研究 有听力损失和没有听力损失的老年人的ICC分为三种 类别：1）完整性，2）连通性的变化，以及3） 抑制性神经递质系统的形态学。 所有形态学 研究将根据ICC的音位结构将其细分为 高频和低频区域。 ICC的完整性将取决于 测量神经元的数量和大小以及ICC的体积， 光镜水平，并通过描述神经元形态学的变化， 在电子显微镜水平上。 注射HRP的小鼠，在项目中研究 3用单单位生理技术，将其用于标测 将生理功能与ICC中的解剖位置相关联。 连接 ICC的大小将通过量化高尔基体中的树突程度来确定， 浸渍的材料，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 体和传出终末的数量，用HRP注射 ICC将被量化。 同样在C57 BL/6 J小鼠中， 树突树和重组的HRP充满传入将进行研究 以确定年龄相关的色调的形态学基础， 重组ICC。 抑制功能的形态学相关因素 在ICC中，将在染色材料中进行化学染色， GABA和甘氨酸的神经递质系统。 数量的 化学染色的终末和细胞体及细胞大小 尸体将被量化。 此外，有限数量的形态学 研究将在上级橄榄复合体（SCC）中进行， 对ICC的重要贡献。 这些研究将包括测量 Nissi染色材料中神经元的数量和大小， 化学染色材料，作为 SOC的形态学上可识别的亚核。

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.