Physiological Consequences of Glutamate Receptor Modulation

谷氨酸受体调节的生理后果

基本信息

项目摘要

The long-term goal of this project is to reveal how neuronal activity produces a lasting change in synaptic transmission and subsequently alters the electrical signaling in a neuronal network. One fundamental feature of the central nervous system is that neuronal activity can modify the characteristics of the postsynaptic response. This use-dependent change in synaptic strength may alter information processing in a neuronal circuit and information storage within the brain. One of the proposed mechanisms for synaptic plasticity is that AMPA-type glutamate receptors present in the postsynaptic membrane undergo dynamic changes in response to alterations in synaptic activity. Alterations in the number of AMPA receptors and in their phosphorylation state can change the amplitude of the synaptic current and thereby alter the postsynaptic response. Recent work by Dr. Liu and her colleague has shown that the repetitive synaptic activation of a subset of AMPA receptors that are permeable to Ca2+ results in the rapid appearance of Ca2+-impermeable synaptic AMPA receptors in a cerebellar interneuron, the stellate cell. This switch not only reduces the amplitude of the synaptic current, but also prolongs the decay time course of the synaptic current. Interestingly, the reversal of this process, changing from Ca2+-impermeable to Ca2+-permeable AMPA receptors, occurs after epileptic seizures. This change may be involved in the pathogenesis of ischemia-induced neuronal death.With National Science Foundation support, Dr. Liu will study the physiological consequences of the activity-dependent switch in AMPA receptor subtypes. This investigation could further our understanding of how synaptic plasticity may alter input-output relationships within a cerebellar neuronal network that is essential for several forms of well characterized motor learning. This study may also increase our understanding of cellular mechanisms underlying neurological disorders associated with excessive activation of Ca2+-permeable AMPA receptors.
该项目的长期目标是揭示神经元活动如何在突触传递中产生持久的变化,并随后改变神经元网络中的电信号。中枢神经系统的一个基本特征是神经元活动可以改变突触后反应的特征。这种突触强度的使用依赖性变化可能会改变神经元回路中的信息处理和大脑中的信息存储。突触可塑性的机制之一是存在于突触后膜中的AMPA型谷氨酸受体响应于突触活动的改变而发生动态变化。AMPA受体数量及其磷酸化状态的改变可以改变突触电流的幅度,从而改变突触后反应。刘博士和她的同事最近的工作表明,对Ca 2+可渗透的AMPA受体子集的重复突触激活导致小脑中间神经元(星状细胞)中Ca 2+不可渗透的突触AMPA受体的快速出现。这种开关不仅降低了突触电流的幅值,而且缩短了突触电流的衰减时间。有趣的是,这个过程的逆转,从Ca 2+不渗透的钙渗透AMPA受体,发生癫痫发作后。在美国国家科学基金会的支持下,刘博士将研究AMPA受体亚型中活性依赖性开关的生理后果。这项研究可以进一步了解突触可塑性如何改变小脑神经元网络内的输入-输出关系,这对几种形式的运动学习是必不可少的。这项研究也可能增加我们对神经系统疾病的细胞机制的理解,这些神经系统疾病与钙渗透性AMPA受体的过度激活有关。

项目成果

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Siqiong Liu其他文献

Siqiong Liu的其他文献

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{{ truncateString('Siqiong Liu', 18)}}的其他基金

Physiological Consequences of Glutamate Receptor Modulation
谷氨酸受体调节的生理后果
  • 批准号:
    0344559
  • 财政年份:
    2004
  • 资助金额:
    $ 5.52万
  • 项目类别:
    Continuing Grant

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