Glutamate receptors in auditory neurons

听觉神经元中的谷氨酸受体

• 批准号: 6837096
• 负责人: LAURENCE O TRUSSELL
• 金额: $ 30.92万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6837096
• 关键词: NMDA receptors; auditory nuclei; chick embryo; cochlear nerve; confocal scanning microscopy; dendrites; glutamate receptor; glutamates; hearing; neurons; receptor expression; synapses; voltage /patch clamp

DESCRIPTION (provided by applicant): In late embryogenesis, the auditory nerve forms synaptic contacts on bushy neurons, producing what will become some of the most highly specialized synapses in the brain. During this early period of development, these terminals generate a cadre of morphological specializations and selective expression of key neurotransmitter receptors that are absolutely essential to auditory processing in the adult. How does this happen? In this proposal, we focus on a striking event in the developmental of the relay: many of the initial synaptic contacts utilize the NMDA receptor for transmission, but over a period of just days these synapses or their receptors are nearly completely removed. NMDA receptors, which are receptors for the transmitter glutamate, are well known to mediate or regulate a variety of cellular processes in development and in adults, due primarily to their unusual voltage dependence and their ability to cause increases in the second messenger Ca 2+. Yet, because of their slow channel kinetics, they are poorly suited to the relay function of these synapses. Rather, these receptors could play a major role in formation of auditory synapses and circuits. We will examine several aspects of the function of these receptors in young chick cochlear nucleus and test hypotheses related to their mechanisms of removal. In particular, we will monitor the formation of a unique subpopulation of synapse that almost exclusively utilizes the NMDA receptor and determine the location of these synapses on the dendritic tree. We intend to find out how these receptors contribute to electrical responses believed to occur in embryos, since much evidence suggests this activity is also an important determinative factor in auditory function. Possible mechanisms for removal of supernumerary synaptic contacts in development will be tested, which may require the NMDA receptor. Finally we will conduct experiments in which the function of NMDA receptors are blocked in vivo, and assay how this manipulation alters the course of development. The results of this study should reveal how expression and regulation of a major transmitter receptor guides formation of an important neuronal element of the auditory system and provide clues as to the functional significance of auditory nerve activity in young animals prior to the onset of hearing.

描述（由申请人提供）：在胚胎发生晚期，听觉神经在浓密的神经元上形成突触接触，产生大脑中一些最高度专业化的突触。在发育的早期阶段，这些终端产生了一系列形态学特化和关键神经递质受体的选择性表达，这对于成人的听觉处理至关重要。这是怎么发生的？在这项提议中，我们重点关注中继发育过程中的一个引人注目的事件：许多最初的突触接触利用 NMDA 受体进行传输，但在短短几天内，这些突触或其受体几乎完全被移除。 NMDA 受体是递质谷氨酸的受体，众所周知，它可以介导或调节发育和成人中的多种细胞过程，这主要是由于其不寻常的电压依赖性及其导致第二信使 Ca 2+ 增加的能力。然而，由于它们的通道动力学缓慢，它们不太适合这些突触的中继功能。相反，这些受体可能在听觉突触和电路的形成中发挥重要作用。我们将检查这些受体在幼鸡耳蜗核中的功能的几个方面，并测试与其去除机制相关的假设。特别是，我们将监测几乎专门利用 NMDA 受体的独特突触亚群的形成，并确定这些突触在树突树上的位置。我们打算找出这些受体如何促进胚胎中发生的电反应，因为许多证据表明这种活动也是听觉功能的重要决定因素。将测试在发育过程中去除多余突触接触的可能机制，这可能需要 NMDA 受体。最后，我们将进行体内阻断 NMDA 受体功能的实验，并分析这种操作如何改变发育过程。这项研究的结果应该揭示主要递质受体的表达和调节如何引导听觉系统重要神经元元件的形成，并为幼年动物在出现听力之前听觉神经活动的功能意义提供线索。