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.

老年性耳聋或老年性听力损失是一种复杂的疾病，影响着美国30%的65岁至74岁的人口，以及至少50%的75岁及以上的人口。听觉功能的缓慢退化表现为言语理解的缺陷，尤其是在嘈杂的环境中。无法处理言语是导致老年人倾向于退出积极参与社会的一个促成因素。对中枢听觉结构的研究发现，抑制性神经递质在频率响应区域的确定、动态范围的控制、噪声中信号的检测、声音在空间中的定位和回声抑制等方面起着至关重要的作用。这些信号的正确编码可能容易受到老化过程的影响。在前一次赠款期间完成的研究发现，与耳蜗背核甘氨酸能神经传递以及下丘GABAA受体的亚单位组成和药理学有关的显着年龄相关变化。衰老在一定程度上可以被认为是一种缓慢渐进的外周去传入。与老年动物中枢听觉通路的研究结果类似，噪音创伤研究和耳朵创伤动物的听觉皮质具有显著的可塑性，暗示着GABA功能的下调。拟议的研究将检验抑制性神经递质GABA在初级听觉皮质(A1)中的作用与年龄相关的变化。初步数据提示A1区的层特异性、年龄相关、突触前和突触后的GABA变化与GABA功能的改变一致。拟议的研究将描述在存在GABA合成酶、亚单位组成和A1 GABAA受体药理学的情况下，蛋鸡特定的、与年龄相关的变化。单单元研究将检查A1神经元反应特性的层特异性、年龄相关的变化，以及它们对GABAA拮抗剂和亚单位选择剂的反应的变化。我们希望在A1神经元的反应特性和药理学中发现反映层特异性的分子和神经化学变化。总的来说，这些研究应该有助于表征衰老对A1抑制电路的影响。了解老年GABAA受体的功能和组成可能会导致针对部分老年性耳聋患者的选择性药物治疗的发展。