MICROCHEMISTRY OF THE COCHLEAR NUCLEUS

耳蜗核的微化学

• 批准号: 3215969
• 负责人: DONALD A. GODFREY
• 金额: $ 19.47万
• 依托单位: UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-12-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3215969
• 关键词: acetylcholine; adenosine triphosphate; aspartate; aspartate transaminase; auditory nuclei; auditory pathways; cats; choline acetyltransferase; cholinergic receptors; cochlea; creatine phosphate; electron microscopy; gamma aminobutyrate; glutamate decarboxylase; glutamates; glutaminase; glycine; high performance liquid chromatography; immunocytochemistry; laboratory rat; lactate dehydrogenases; malate dehydrogenase; neural transmission; neuroanatomy; neurochemistry; neurotransmitter metabolism; neurotransmitters; olivary body; stereotaxic techniques; synapses; taurine

Diagnosis of hearing disorders of central origin is in a primitive state, largely because our understanding of the auditory system decreases markedly as one moves centrally from the cochlea. Probably many subtle central auditory disorders have yet to even be described. Foundational for understanding the function of any part of the brain is knowledge of its chemistry. Both medical and illicit use of drugs have demonstrated that chemical imbalances can dramatically affect behavior of all types. Chemical imbalances in the central auditory pathways would be expected to result in faulty processes of information about the sound environment, and might manifest themselves, not as loss of hearing, but as distorted hearing, including perception of sounds not actually present (e.g., tinnitus or hallucinations) or misinterpretation of environmental sounds. Since the auditory system is so fundamental to human communication, it may not be too far-fetched to suggest that some individuals classified as mentally disturbed may be suffering from a chemical disorder of the central auditory system. Many chemical imbalances that affect behavior involve communication between neurons, which has been found to involve chemical transmitters at virtually all synaptic junctions in mammals. This proposal constitutes a step in a long-range effort to understand the chemistry of the cochlear nucleus, the first brain center of the auditory system. Neurotransmitter chemistry will be emphasized, especially that of acetylcholine, which has been well-established for many years at autonomic and neuromuscular synapses, and the amino acids aspartate, glutamate, glycine and gamma-aminobutyrate, which may be the most prominent transmitter in the brain. In order to reach a functional appreciation for the chemistry, close correlations with anatomical and physiological findings are necessary. In the proposed work, quantitative histochemistry, involving chemical determinations for microscopic pieces of tissue, and high-resolution immunohistochemistry will be combines with tract-tracing anatomy to provide insights about the magnitudes, sources and terminations of cholinergic and amino acid pathways related to the cochlear nucleus. Effects of acetylcholine and amino acid transmitters and related drugs on cochlear nucleus neurons will be studied using an in vitro slice preparation. The microchemistry of the slices will begin to be evaluated, especially for amino acids. Release of amino acids from the slices and their quantitative distributions within the slices will be measured.

诊断中心渊源的听力障碍处于原始状态， 主要是因为我们对听觉系统的理解明显降低 当人们从耳蜗中心移动时。 大概有许多微妙的中央 听觉障碍尚未描述。 基础 了解大脑任何部分的功能是对其的知识 化学。 医疗和非法使用药物都表明 化学失衡会极大地影响所有类型的行为。 预计中央听觉途径中的化学失衡将 导致有关声音环境的信息的错误过程，以及 可能表现出来，不是失去听力，而是扭曲 听力，包括对声音的看法实际上没有的（例如， 耳鸣或幻觉）或误解环境声音。 由于听觉系统对人类交流至关重要，因此 不要太牵强 精神上的干扰可能患有中央的化学障碍 听觉系统。 影响行为的许多化学失衡涉及 神经元之间的通信，已发现涉及化学 几乎所有哺乳动物的突触连接处的发射器。 这个建议 构成了远程努力以了解化学的一步 耳蜗核，听觉系统的第一个大脑中心。 将强调神经递质化学，尤其是 乙酰胆碱，在自主教中已经建立了许多年 和神经肌肉突触，以及氨基酸天冬氨酸，谷氨酸， 甘氨酸和γ-氨基丁酸，这可能是最突出的 大脑中的发射器。 为了实现功能上的欣赏 化学，与解剖学和生理的密切相关 发现是必要的。 在拟议的工作中，定量组织化学， 涉及微观组织的化学测定，以及 高分辨率免疫组织化学将与道追踪结合在一起 解剖学提供有关大小，来源和终止的见解 与耳蜗核有关的胆碱能和氨基酸途径。 乙酰胆碱和氨基酸发射器以及相关药物对 将使用体外切片研究耳蜗核神经元 准备。 切片的微化学将开始评估， 特别是对于氨基酸。 从切片中释放氨基酸， 将测量它们在切片中的定量分布。