Glutamate Gated Channels in Central & Peripheral Neurons

描述（由申请人提供）：我的工作的长期目标是 通过研究突触传递， NMDA、AMPA和红藻氨酸受体的操作，这些受体形成离子通道门控 被神经递质谷氨酸所控制另一个主要目标是发现 这些受体可能允许临床干预， 兴奋性毒性细胞死亡或提供镇痛。中概述的实验 本申请集中于红藻氨酸受体组成的调节 AMPA受体亚细胞分布的调节。一系列 神经元红藻氨酸受体的电生理学研究 海马、脊髓和背根神经节，我们已经证明， 这些细胞群表达具有不同药理学活性的红藻氨酸受体 特性.具体目标1的实验将使用分子生物学， 生理学和亚基缺陷小鼠，以研究 这些差异。具体目标2侧重于特定红藻氨酸盐的作用 脊髓突触传递中的受体亚单位。我们最近 展示了红藻氨酸受体参与的三种不同方式 脊髓背角的突触传递。实验 这一目标将试图确定G1uR5或G1uR6亚基是否 所需的突触后红藻氨酸受体介导的一个组成部分， 初级传入传递，或突触前红藻氨酸受体， 调节初级传入神经和脊髓神经递质的释放 中间神经元。本申请的第三个主要目的是研究 海马神经元上谷氨酸受体分布的调控 分子量GTribrab 5和内吞运输的其他组分 通路

DESCRIPTION (provided by applicant): The long-term objective of my work is to provide a better understanding of synaptic transmission by studying the operation of NMDA, AMPA, and kainate receptors, which form ion channels gated by the neurotransmitter glutamate. Another major goal is to uncover properties of these receptors that may allow for clinical intervention to prevent excitotoxic cell death or to provide analgesia. The experiments outlined in this application focus on the regulation of kainate receptor composition and on the regulation of AMPA receptor sub-cellular distribution. In a series of studies on the electrophysiology of kainate receptors in neurons from the hippocampus, spinal cord and dorsal root ganglia, we have shown that each of these cell populations express kainate receptors with distinct pharmacological properties. The experiments in Specific Aim 1 will use molecular biology, physiology and subunit deficient mice to investigate the structural basis for these differences. Specific Aim 2 is focused on the role of specific kainate receptor subunits in spinal synaptic transmission. We have recently demonstrated three different ways in which kainate receptors participate in synaptic transmission in the dorsal horn of the spinal cord. Experiments in this aim will seek to determine whether the G1uR5 or GIuR6 subunits are required for the postsynaptic kainate receptors that mediate a component of primary afferent transmission, or for the presynaptic kainate receptors that modulate transmitter release from primary afferents and from spinal interneurons. The third major Aim of this application is to investigate the control of glutamate receptor distribution on hippocampal neurons by the low molecular weight GTPase rab 5 and other components of the endocytic trafficking pathway.