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.

老年性耳聋或与年龄相关的听力损失是一种复杂的疾病，影响30%的65至74岁的美国人口，以及至少50%的75岁及以上人口。 听觉功能的缓慢退化通过言语理解的缺陷表现出来，特别是在嘈杂的环境中。 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，抑制性神经递质在确定频率响应区域、控制动态范围、检测噪声中的信号、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易受老化过程的影响。 在上一个资助期内完成的研究发现，与耳蜗背核中的甘氨酸能神经传递以及下丘中GABAA受体的亚基组成和药理学相关的显著年龄相关变化。 衰老在某种程度上可以被认为是一种缓慢进行的外周神经传入阻滞。 与老年动物的中枢听觉通路中的发现类似，噪声创伤研究和耳朵创伤的动物显示听觉皮层具有显著的可塑性，提示GABA功能下调。 拟议的研究将检查初级听觉皮层（A1）中抑制性神经递质GABA作用的年龄相关变化。 初步数据表明，层特定的，年龄相关的，突触前和突触后GABA的变化A1与GABA功能的改变相一致。 拟议的研究将表征层特定的，年龄相关的变化中存在的合成酶的GABA，亚基化妆品，和药理学的A1 GABAA受体。 单一单位的研究将检查层特异性，年龄相关的A1神经元的响应特性的变化，并在其响应GABAA拮抗剂和亚基选择剂的变化。 我们希望找到层特异性的分子和神经化学变化反映在A1神经元的响应特性和药理学。总的来说，这些研究应该有助于表征老化对A1抑制回路的影响。 了解老年人GABAA受体的功能和组成可能会导致老年人个体子集的选择性药物治疗的发展。