REGULATION OF SYNAPTIC AMINO ACID RECEPTORS

突触氨基酸受体的调节

• 批准号: 6187255
• 负责人: LAURENCE O TRUSSELL
• 金额: $ 18.76万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-05-01 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6187255
• 关键词: action potentials; auditory nuclei; brain electrical activity; calcium flux; chick embryo; electrophysiology; embryo /fetus cell /tissue; evoked potentials; glia; glutamate receptor; glutamate transporter; membrane potentials; neural inhibition; neural transmission; neuroregulation; neurotransmitter transport; receptor sensitivity; synapses; tissue /cell culture; voltage /patch clamp

The control of the strength of individual synapses is essential to fine- tuning the performance of neural circuits. Synaptic strength may be regulated in the short term by trains of high frequency pre-synaptic action potential which at many synapses leads to short-term synaptic depression. Using the large calyceal synapses of the chick cochlear nucleus (nucleus magnocellularis, or nMAG), we will carry out experiments which are based upon the following hypothesis: We propose that there are multiple forms of short-term depression, each with distinctive properties, and that these become recruited at specific frequencies of neural activity. By the independent regulation of these forms of depression, neurons may produce changes in synaptic strength at specific ranges of frequencies and not at others. This concept, which we term complex depression, would provide a powerful and sophisticated means for control of neural circuits, and will be comprehensively tested in the proposed studies. These will employ patch clamp recordings and the direct measurement of pre- and postsynaptic signals during the course of depression, testing specific hypotheses about the types, origins and function of depression. Specifically, we will first document that there are different components to depression and how each contributes to the control of synaptic strength at specific frequencies of synaptic activity. Then, we will identify the probable cellular mechanisms that underlie different forms of depression. Moreover, we will examine how depression can be regulated by transmitter uptake systems and by patterns of activity. Finally, we will determine the functional consequences of depression when synapses converse onto a single target cell. The results of the analyses will give new insight into the factors that determine the optical transmission of signals in the brain, and will contribute to an understanding of sensory or cognitive deficits.

对单个突触强度的控制对于精细的- 调节神经回路的性能。突触强度可能是 在短期内由高频率突触前神经元调控， 动作电位，在许多突触导致短期突触 萧条利用小鸡耳蜗的大的萼状突触 核（大细胞核，或nMAG），我们将进行 基于以下假设的实验：我们建议 有多种形式的短期抑郁症，每一种 独特的属性，这些被招募在特定的 神经活动的频率通过这些独立的监管， 抑郁症的形式，神经元可能会产生突触强度的变化， 特定频率范围，而不是其他频率。这个概念，我们 复杂抑郁症，将提供一个强大而复杂的 控制神经回路的方法，并将进行全面测试 在拟议的研究中。这些将采用膜片钳记录， 直接测量突触前和突触后信号， 抑郁症的过程，测试关于类型的特定假设， 抑郁症的起源和功能具体来说，我们将首先记录 抑郁症有不同的组成部分， 有助于控制特定频率的突触强度 突触活动。然后，我们将确定可能的细胞 不同形式的抑郁症背后的机制。而且我们 将研究抑郁症是如何通过神经递质的摄取来调节的， 系统和活动模式。最后，我们将确定 当突触匡威到一个 单个靶细胞。分析的结果将提供新的见解 的因素，决定了光传输的信号， 大脑，并将有助于理解感官或 认知缺陷