Coding in Auditory Neurons: Effects of Amino Acids

听觉神经元的编码：氨基酸的作用

• 批准号: 6640280
• 负责人: Donald M. Caspary
• 金额: $ 32.08万
• 依托单位: SOUTHERN ILLINOIS UNIVERSITY SCH OF MED
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-08-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6640280
• 关键词: GABA receptor; aging; auditory nuclei; autoradiography; electrophysiology; gamma aminobutyrate; glutamate decarboxylase; glycine; immunocytochemistry; in situ hybridization; inferior colliculus; laboratory rat; neural transmission; neurochemistry; neurotransmitter metabolism; presbycusis; receptor binding; receptor expression; sound perception

Presbycusis or age-related hearing loss is a complex disorder affecting 30 percent of the United States population aged 65 to 74 years, and at least 50 percent of the population 75 years of age and older. Slow deterioration of auditory function manifests itself through deficits in speech comprehension, especially in noisy environments. Inability to process speech is a contributing factor leading to a tendency of elderly individuals to withdraw from active participation in society. Studies in central auditory structures have found that inhibitory neurotransmitters are critically involved in determination of the frequency response area, control of dynamic range, detection of signals in noise, localization of sound in space and echo suppression. Proper coding of these signals may be vulnerable to the aging process. Studies completed during the previous grant period found significant age-related changes related to glycinergic neurotransmission in the dorsal cochlear nucleus and in the subunit makeup and pharmacology of the GABAA receptor in the inferior colliculus. Aging can be thought of, in part, as a slow progressive peripheral deafferentation. Similar to findings in the central auditory pathway of aged animals, noise trauma studies and animals with traumatized ears show significant plasticity in auditory cortex suggestive of a down regulation of GABA function. Proposed studies will examine age-related changes in the role of the inhibitory neurotransmitter GABA in primary auditory cortex (A1). Preliminary data are suggestive of layer specific, age-related, pre- and postsynaptic GABA changes in A1 consistent with altered GABA function. Proposed studies will characterize layer-specific, age-related changes in the presence of the synthetic enzyme for GABA, the subunit makeup, and the pharmacology of A1 GABAA receptors. Single unit studies will examine layer-specific, age-related changes in the response properties of A1 neurons and changes in their responses to GABAA antagonists and subunit selective agents. We expect to find layer-specific molecular and neurochemical changes reflected in the response properties and pharmacology of A1 neurons. Collectively, these studies should help characterize the impact of aging on inhibitory circuits in the A1. Understanding the function and the makeup of the aged GABAA receptor could lead to the development of selective pharmacotherapy for a subset of presbycusic individuals.

长老会或与年龄相关的听力损失是一种复杂的疾病，影响了65至74岁的美国人口的30％，至少50％的人口75岁及以上。 听觉功能的缓慢恶化通过语音理解的缺陷表现出来，尤其是在嘈杂的环境中。 无法处理言论是导致老年人从积极参与社会的倾向的趋势。中央听觉结构中的研究发现，抑制性神经递质与确定频率响应区域，动态范围的控制，噪声中信号的检测，空间中的声音定位和回声抑制。 这些信号的正确编码可能容易受到老化过程的影响。 在上一个赠款期间完成的研究发现，在背部耳蜗核中与糖神经传递有关的年龄相关变化以及在下丘中GABAA受体的亚基化妆和药理学中的研究。 可以将衰老视为缓慢的渐进外围脱落。 与年龄动物的中央听觉途径中的发现相似，噪声创伤研究和具有创伤性耳朵的动物在听觉皮层中显示出明显的可塑性，这表明对GABA功能的调节下降。 拟议的研究将检查与年龄相关的抑制性神经递质GABA在原发性听觉皮层（A1）中的作用变化。 初步数据暗示了层特异性，与年龄相关的，与GABA函数一致的A1中的突触前和突触后GABA变化。 拟议的研究将表征GABA合成酶，亚基化妆和A1 GABAA受体的药理的合成酶的存在。 单个单元研究将检查A1神经元的响应特性的层特异性，年龄相关的变化，以及它们对GABAA拮抗剂和亚基选择性剂的反应变化。 我们希望找到反应特异性的分子和神经化学变化，这些变化反映在A1神经元的反应特性和药理学中。总的来说，这些研究应有助于表征衰老对A1抑制回路的影响。 了解老年GABAA受体的功能和构成可能导致为长期个体的一部分提供选择性药物疗法。