AGE RELATED SYNAPTIC CHANGES IN THE AUDITORY BRAINSTEM

老年性听力损失(老年性耳聋)是主要的沟通障碍 在工业化社会中是仅次于关节炎的第二大疾病 对65岁以上的人的生活质量的影响。不成比例的贫穷 言语辨别，特别是在存在背景噪音的情况下 年龄相关性听力损失的一个特征，被认为反映了， 在一定程度上，这是中枢听觉系统的变化。下丘 (IC)由三个主要部分组成，背侧皮质， 外皮质、外皮质和中央核，并且是 一个关键的听觉中脑处理中心，用于提升和 下行的听觉通路。中枢神经系统中的神经元执行空间和 复杂信号的时间编码，声音定位，以及可能 参与提取嵌入噪声的声学信号。这个 神经递质γ-氨基丁酸(GABA)、甘氨酸和 兴奋性氨基酸(EaAs)已被证明是编码许多 在IC的这些重要的听觉任务中。最近，一些人 神经化学和免疫细胞化学研究，以及初步的 这项赠款的研究表明，GABA介导的年龄相关性下降 抑制，EAA受体水平的改变，以及 类似于使用EAA的“兴奋型”突触前终末 神经递质。甘氨酸的显著但较小的损失也是 据报道。这些损失或不平衡可能损害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界定与年龄有关的变化。 在抑制和兴奋编码的突触组织中 IC中有两个不同的频率区域。与年龄相关的突触变化将 在耳蜗核(CN)也进行了评估，并与 在IC中描述的，其预测的主要目标。对于每个IC 而CN的细分，突触前后的年龄相关性变化将 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解决以下问题 问题：1)GABA和/或甘氨酸是否存在与年龄相关的减少- 免疫反应终末？2)是否有年龄相关的变化 GABA和甘氨酸末端接触特定神经元区域(即， 体细胞和各种口径的树突)，这将反映 GABA能突触输入分布的相应变化 “兴奋型”终端也有类似的变化吗？ 三种终末类型的形态与年龄相关的变化是 GABA、甘氨酸和EAA的数量和分布随年龄的变化 受体？6)GABAA和GABAA模式是否有年龄相关的变化 谷氨酸受体亚单位表达？对Pre-And和 突触后底物的年龄相关性抑制和兴奋变化 将增进我们对中枢性老年性耳聋的认识和 将使我们能够随后探索这些问题背后的机制 为实现长远发展目标而努力的变化 某些类型老年性痴呆的药物治疗 精神错乱。

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.