ANATOMY OF THE AUDITORY SYSTEM

本研究的重点是哺乳动物耳蜗核的突触巢。 统一的假设是，巢的结构，以介导的塑料变化，以响应声学过度刺激和损害的听觉系统。这些新发现的巢由紧密堆积的突触末端的聚集体组成，这些突触末端不被神经胶质过程彼此分开是不寻常的。 巢发生在整个耳蜗核，并可能达到其最大的发展在人类。 它们的精细结构和缺乏具有高亲和力谷氨酸转运蛋白的星形胶质细胞过程可能赋予巢一个不寻常的潜力，产生塑料变化，以持续的刺激和破坏性的噪音水平。 一个具体的假设是，过度刺激产生结构和组织化学变化，包括慢性变性和新的增长的突触末梢在巢和与他们相关的地区。 为了了解兴奋性和抑制性输入的平衡是否因此而受到干扰，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，它们的起源，以及它们在响应噪声损伤时所经历的塑性变化。 电子显微镜将用于表征的精细结构和量化类型的突触末梢在巢的灰鼠和小鼠耳蜗核。 每种类型的结局的主要输入的来源将确定与顺行标记和银退化的方法。 免疫细胞化学和原位杂交将用于识别与每种类型的结束相关的传递相关分子。 这些规范性数据将被用作确定暴露于噪声后巢中的结束类型的相对比例的变化的基础。 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，包括插入小损伤、细胞或乳胶微球以递送生长因子，以及单基因缺失或过表达。 这些变化可能解释了噪声引起的人类神经性耳聋的一些听觉功能障碍，包括耳鸣和响度招募。 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.