NEUROTRANSMITTERS IN THE AUDITORY SYSTEM

听觉系统中的神经递质

• 批准号: 3216087
• 负责人: STEVEN J POTASHNER
• 金额: $ 21.6万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-12-01 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3216087
• 关键词: acetylcholine; aspartate; auditory feedback; auditory nuclei; auditory pathways; autoradiography; cochlear lesion; cysteine; gamma aminobutyrate; glutamates; glycine; guinea pigs; homocysteine; neural information processing; neurochemistry; neurotransmitter receptor; neurotransmitters; noise biological effect; synapses

A dynamic relationship is hypothesized between the auditory periphery and the regulation of synaptic biochemistry in pathways of the central auditory nervous system. This predicts that changes in the acoustic efficacy of the ear, for example, after the cochlear trauma or long exposure to abnormally low or high levels of sound, should adjust the synaptic biochemistry of auditory pathways. Persistent changes of synaptic structure in the medial nucleus of the trapezoid body and of neuronal discharge in the inferior colliculus, medial geniculate nucleus, and auditory cortex were reported after procedures that decrease the acoustic efficacy of one ear. These changes may reflect a regulatory process that begins in the ascending brain stem auditory pathways. Knowledge of these phenomena will be valuable in understanding the synaptic basis of auditory functions, controlling pathology, and rehabilitating the central auditory system after insult. We propose to elucidate the hypothesized regulatory relationship. FIRST, we will identify the ascending auditory brain stem projections that use transmitters such as glutamate, aspartate, homocysteic acid, cysteine sulfanilic acid, GABA, glycine, and acetylcholine. Transmitters have been suggested for only one or two of the ascending auditory pathways. To determine the transmitters used by the others, ascending tracts will be lesioned to destroy their synaptic endings. At each projection site, we will measure changes in the evoked release and the high affinity uptake of the putative transmitters and quantify the binding activity of synaptic receptors. SECOND, we will determine the effect of cochlear lesions on the synaptic transmitter biochemistry in the brain stem auditory nuclei. High frequency hearing loss will be produced by acoustic trauma and surgical lesions of the cochlea. Then, synaptic biochemical activities, such as transmitter release, high-affinity uptake, and receptor binding, will be compared in the projection sites of the ascending auditory pathways of hearing-impaired and unlesioned cases. THIRD, we will determine the effect of exposure to different levels of sound on the synaptic transmitter biochemistry in the brain stem auditory nuclei. Three levels of environmental noise will provide different levels of cochlear activity without cochlear damage. We will compare synaptic biochemical activities in animals with bilateral ossiculectomies, intact animals kept in a 'normal' environment, and intact animals kept in a 'noisy' environment.

在听觉外围和 中央听觉途径中突触生物化学的调节 神经系统。 这预示着变化 例如，耳蜗创伤或长期暴露于异常之后 低或高的声音应调整 听觉路径。 内侧突触结构的持续变化 梯形体的核和下部神经元排出的核 据报道，丘丘，内侧基因核和听觉皮层 经过降低一只耳朵的声学功效的程序。这些 变化可能反映了从上升大脑开始的调节过程 STEM听觉途径。对这些现象的了解将很有价值 了解听觉功能的突触基础，控制 侮辱后的病理学并修复中央听觉系统。 我们建议阐明假设的监管关系。第一的， 我们将确定使用的上升听觉脑干预测 发射器，例如谷氨酸，天冬氨酸，同型拟南芥，半胱氨酸 亚磺酸，GABA，甘氨酸和乙酰胆碱。发射器已经过去了 仅建议使用一两个上升的听觉途径。到 确定其他人使用的发射器，上升区将是 病变破坏了他们的突触结局。在每个投影站点，我们 将衡量诱发释放的变化和高亲和力的吸收 推定的发射器并量化突触的结合活性 受体。其次，我们将确定耳蜗病变对 脑干听觉核中的突触发射器生物化学。高的 听力损失将由声学创伤和手术产生 耳蜗病变。然后，突触生化活动，例如 发射机释放，高亲和力摄取和受体结合，将是 在上升听觉途径的投影位点进行了比较 听力障碍和无效案件。第三，我们将确定效果 突触发射器上接触不同水平的声音 脑干听觉核中的生物化学。三个级别 环境噪声将提供不同水平的人工耳蜗活动 没有人工耳蜗。我们将比较突触生化活动 在具有双侧骨切除术的动物中，完整的动物保存在 “正常”环境，完整的动物保存在“嘈杂”的环境中。