AGE RELATED SYNAPTIC CHANGES IN THE AUDITORY BRAINSTEM

老年性听力损失（老年性耳聋）是主要的交流障碍 是工业化社会的第二大疾病，仅次于关节炎疾病。 对65岁以上人群生活质量的影响。 不对称性差 语音辨别，特别是在存在背景噪声的情况下， 这是年龄相关性听力损失的一个特征， 部分是因为中央听觉系统的改变 下丘 (IC)由三个主要的分支组成，背侧皮层， 外皮层，外皮层，中央核， 一个关键的听觉中脑处理中心， 下行听觉通路 IC中的神经元执行空间和 复杂信号的时间编码，声音定位，可能是 参与提取嵌入噪声中的声学信号。 的 神经递质γ-氨基丁酸（GABA），沿着的是甘氨酸和 刺激性氨基酸（EAA）已被证明是编码许多蛋白质所必需的。 这些重要的听觉任务。 近日多家 神经化学和免疫细胞化学研究，以及初步的 这项研究表明，GABA介导的 抑制，EAA受体水平的改变，以及 类似于使用EAA的“兴奋型”突触前末梢 神经传递素 甘氨酸的显著但较小的损失也被发现。 报道 这些损失或不平衡可能会损害IC功能， 降低了在噪声中检测信号和定位声音的能力。 本研究的目的是进一步确定与年龄有关的变化 在抑制性和兴奋性编码的突触组织中， IC中的两个不同频率区域。 与突触相关的变化将 也可以在耳蜗核（CN）中进行评估，并与那些 在IC中描述，其预测的主要目标。 对于每个IC 和CN细分，突触前和突触后年龄相关的变化将是 使用定量免疫金电子显微镜检查，定量 受体放射自显影和原位杂交，以解决以下问题 问题：1）是否存在与年龄相关的GABA-和/或甘氨酸-减少？ 免疫反应终末？2)是否有与年龄相关的数字变化 GABA和甘氨酸末端接触特定的神经元区域（即， 胞体和各种口径的树突），这将反映一个 GABA能突触输入分布的相应变化？ 第三章 是否有类似的变化与“兴奋型”终端”4）是否有 年龄相关的变化形态的三个终端类型？5)是 GABA、甘氨酸和EAA数量和分布的年龄相关变化 受体？ 6)GABAA的模式是否存在与年龄相关的变化， 谷氨酸受体亚单位表达 前知后觉， 年龄相关的抑制和兴奋变化的突触后底物 在IC和CN将提高我们对中央性老年性耳聋的理解， 将使我们能够随后探索这些潜在的机制， 为了实现我们的长远目标， 药物治疗某些类型的与年龄有关的交流 紊乱

Age-related hearing loss (presbycusis) is the major communication disorder of industrialized society and is second only to arthritic diseases in its impact on the quality of life for people over 65. Disproportionately poor speech discrimination, particularly in the presence of background noise is one characteristic of age-related hearing loss and is thought to reflect, in part, changes in the central auditory system. The inferior colliculus (IC) is comprised of three major subdivisions, the dorsal cortex, the external cortex, and the external cortex, and the central nucleus, and is a critical auditory midbrain processing center for both ascending and descending auditory pathways. Neurons in the IC perform spatial and temporal coding of complex signals, sound localization, and are probably involved in the extraction of acoustic signals embedded in noise. The neurotransmitter gamma-aminobutyric acid (GABA), along with glycine and the excitant amino acids (EAAs) have been shown to be essential for coding many of these important auditory tasks in the IC. Recently, a number of neurochemical and immunocytochemical studies, as well as the preliminary studies for this grant suggest an age-related decline in GABA-mediated inhibition, alterations in the levels of EAA receptors, and loss of "excitatory-type" presynaptic terminals similar to those that use an EAA neurotransmitter. A significant but smaller loss of glycine has also been reported. These losses or imbalances are likely to impair IC function, degrading the ability to detect signals in noise and localize sounds. The objective of the present study is to further define age-related changes in the synaptic organization underlying inhibitory and excitatory coding in two different frequency areas in the IC. Age-related synaptic changes will also be assessed in the cochlear nucleus (CN) and compared to those described in the IC, the principal target of its projections. For each IC and CN subdivision, pre- and postsynaptic age-related changes will be examined using quantitative immunogold electron microscopy, quantitative receptor autoradiography and in situ hybridization to address the following questions; 1) Are there age-related reductions of GABA- and/or glycine- immunoreactive terminals? 2) Are there age-related changes in the number of GABA and glycine terminals contacting specific neuronal areas (i.e., somata and dendrites of various calibers) that would reflect a corresponding change in the distribution of GABAergic synaptic input? 3) Are there similar changes with "excitatory type" terminals" 4) Are there age-related changes in the morphology of the three terminal types? 5) Are age-related changes in number and distribution of GABA, glycine, and EAA receptors? 6) Are there age-related changes in the patterns of GABAA and glutamate receptor subunit expression? Knowledge of the pre-and postsynaptic substrates of age-related changes in inhibition and excitation in the IC and CN will enhance our understanding of central presbycusis and will allow us to subsequently explore the mechanisms underlying these changes in an effort to achieve our long range goal to develop pharmacotherapies for certain types of ag e-related communicative disorders.