ANATOMY OF THE AUDITORY SYSTEM

这项研究的重点是哺乳动物耳蜗核的突触巢。统一的假设是，鸟巢的结构是为了适应声音过度刺激和对听觉系统的损害而产生的可塑性变化。这些新发现的巢由紧密排列的突触末端聚集组成，这些突触末端不寻常地没有被神经胶质突起分开。这些巢分布在整个耳蜗核，并可能在人类体内达到最大的发育。它们的精细结构和缺乏具有高亲和力谷氨酸转运体的星形细胞突起，可能赋予这些巢不寻常的潜力，使其在持续刺激和破坏性噪音水平上产生可塑性变化。一种特定的假设是，过度刺激会导致结构和组织化学变化，包括巢及其相关区域的突触末端的慢性退化和新的生长。为了了解兴奋性和抑制性输入的平衡是否因此受到干扰，分析将集中在巢中不同类型突触末端的相对比例、与它们相关的递质相关分子、它们的来源，以及它们在噪声损伤时经历的可塑性变化。电子显微镜将被用来描述栗鼠和小鼠耳蜗核巢中的精细结构和突触终末的类型。每种类型结尾的主要输入的来源将用顺行标记法和银退化方法确定。免疫细胞化学和原位杂交将被用来识别与每种类型的末端相关的递质相关分子。这些标准数据将被用作确定暴露在噪声中的巢中末端类型的相对比例变化的基础。这些发现将提示干扰这些末端的退行性和再生性变化的方法，包括插入小病变、细胞或乳胶微球以输送生长因子，以及单基因缺失或过度表达。这些变化可能解释了噪音引起的人类神经性耳聋的一些听觉功能障碍，包括耳鸣和响度恢复。微扰实验应该直接导致对这种疾病的新疗法的建议。

The focus of this research is the synaptic nests of the mammalian cochlear nucleus. The unifying hypothesis is that the nests are structured so as to mediate plastic changes in response to acoustic overstimulation and damage to the auditory system. These newly discovered nests consist of aggregations of closely packed synaptic endings which are unusual in not being separated from each other by glial processes. The nests occur throughout the cochlear nucleus and may reach their greatest development in the human. Their fine structure and lack of astrocytic processes having high-affinity glutamate transporters may endow the nests with an unusual potential for producing plastic changes to ongoing stimulation and to damaging levels of noise. A specific hypothesis is that overstimulation produces structural and histochemical changes, including chronic degeneration and new growth of synaptic endings in the nests and the regions associated with them. To see if the balance of excitatory and inhibitory input is thereby disturbed, the analysis will focus on the relative proportions of the different types of synaptic ending in the nests, the transmitter-related molecules associated with them, their origins, and the plastic changes they undergo in response to noise damage. Electron microcopy will be used to characterize the fine structure and quantify the types of synaptic endings in the nests of the chinchilla and mouse cochlear nucleus. The origins of the major inputs for each type of ending will be determined with anterograde-labeling and silver-degeneration methods. Immunocytochemistry and in situ hybridization will be used to identify the transmitter-related molecules associated with each type of ending. These normative data will be used as a basis for determining changes in the relative proportions of ending types in the nests following exposure to noise. These findings will suggest ways of perturbing the degenerative and regenerative changes of these endings, including the insertion of small lesions, cells or latex microspheres for delivery of growth factors, and single gene deletions or overexpression. These changes may account for some of the auditory dysfunction in human nerve deafness caused by noise, including tinnitus and loudness recruitment. The perturbation experiments should lead directly to proposals for new therapies in this disorder.