METABOTROPIC GLUMATE RECEPTORS IN BASAL GANGLIA

基底节代谢型谷氨酸受体

• 批准号: 7349216
• 负责人: Yoland Smith
• 金额: $ 4.01万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-09 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7349216
• 关键词: basal ganglia; behavioral habituation /sensitization; cocaine; drug abuse; glutamate receptor; interneurons; lenticular nucleus; neural transmission; neurons; nucleus accumbens; play; proteins; role; voltage /patch clamp

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project is composed of various sets of experiments that aim at addressing different aspects of the localization, function and trafficking mechanisms of metabotropic glutamate receptors (mGluRs) in the basal ganglia. This series of studies involve electron microscopic immunogold approaches combined with biochemical immunoblotting techniques, whole cell patch clamp recordings and in vivo behavioral sensitization to cocaine. Over the past year, data obtained in this project can be summarized under the following three specific conclusions: 1) Homer proteins play an important role in regulating the subsynaptic localization and expression of group I mGluRs in the globus pallidus (GP) and subthalamic nucleus (STN), 2) Group II and group III mGluRs play a critical role in regulating excitatory neurotransmission in the GP and 3) Both group I mGluRs are widely expressed in projection neurons and interneurons in the shell and core of the nucleus accumbens where they likely play important function in the addictive properties of drugs of abuse. Together, these findings provide further evidence for the widespread expression and functional importance of mGluRs in basal ganglia. Our data also set the stage for an important contribution of Homer proteins in regulating the trafficking and subcellular distribution of group I mGluRs in the basal ganglia.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。该项目由多组实验组成，旨在解决基底神经节代谢型谷氨酸受体 (mGluR) 的定位、功能和运输机制的不同方面。这一系列研究涉及电子显微镜免疫金方法与生化免疫印迹技术、全细胞膜片钳记录和可卡因体内行为致敏相结合。一年来，本项目获得的数据可概括为以下三个具体结论：1）Homer蛋白在调节苍白球（GP）和丘脑底核中I组mGluRs的突触下定位和表达中发挥重要作用。 STN),2) II 组和 III 组 mGluR 在调节 GP 的兴奋性神经传递中发挥关键作用，3) I 组 mGluR 广泛表达于伏隔核外壳和核心的投射神经元和中间神经元可能在滥用药物的成瘾特性中发挥重要作用。总之，这些发现为 mGluR 在基底神经节中的广泛表达和功能重要性提供了进一步的证据。我们的数据还为荷马蛋白在调节基底神经节中 I 组 mGluR 的运输和亚细胞分布方面的重要贡献奠定了基础。