METABOTROPIC GLUMATE RECEPTORS IN BASAL GANGLIA

基底节代谢型谷氨酸受体

• 批准号: 7715716
• 负责人: Yoland Smith
• 金额: $ 3.56万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715716
• 关键词: Basal Ganglia; Brain; Collaborations; Computer Retrieval of Information on Scientific Projects Database; Corpus striatum structure; Data; Funding; Gene Deletion; Genes; Globus Pallidus; Grant; Immunoelectron Microscopy; In Vitro; Individual; Institution; Interneurons; Italy; Membrane; Metabotropic Glutamate Receptors; Methods; Mus; Parkinson Disease; Parvalbumins; Pharmacotherapy; Physiological; Property; Rattus; Research; Research Personnel; Resolution; Resources; Role; Slice; Source; Synapses; Techniques; United States National Institutes of Health; Universities; mouse model; novel; patch clamp; receptor; trafficking; transmission process

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. In this project we used a combination of high resolution immunoelectron microscopy, patch clamp recording technique and gene deletion method to characterize various aspects of the localization, function and trafficking mechanisms of metabotropic glutamate receptors (mGluRs) in the basal ganglia. Three main studies related to this project have been achieved during the past year. The key findings of these studies can be summarized as follows: (1) In collaboration with Dr Paul Worley at Johns Hopkins University, we have demonstrated that the deletion of Homer genes have significant effects on the expression and the pre-synaptic localization of group I metabotropic glutamate receptors in normal mice and MPTP-treated mice model of Parkinson's disease. (2) Using the in vitro patch clamp recording technique in rat brain slices, we demonstrated that the functional and pharmacological properties of group I mGluRs in the globus pallidus are highly dependent on dopaminergic transmission, suggesting significant functional changes of these receptors in Parkinson's disease. (3) In collaboration with Pisani and colleagues in Italy, we demonstrated a significant degree of co-localization of the two group I mGluRs (mGluR1a and mGluR5) in individual parvalbumin-containing interneurons in the rat striatum. Surprisingly, despite such a high degree of co-existence, in vitro patch clamp recordings showed that activation of mGluR1 only have significant physiological effects on the membrane polarization of these interneurons. These data highlight the complexity and multifarious roles of these receptors in basal ganglia. Together, our findings provide important information on the localization, function and plasticity of group I mGluRs in basal ganglia, a novel highly promising target for Parkinson's disease pharmacotherapy.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 在这个项目中，我们使用了高分辨率免疫电子显微镜，斑块夹记录技术和基因缺失方法来表征基础神经节中代谢性谷氨酸受体（MGLUS）的定位，功能和运输机制的各个方面。在过去的一年中，已经实现了与该项目有关的三项主要研究。这些研究的关键发现可以总结如下：（1）与约翰霍普金斯大学的保罗·沃利博士合作，我们证明，荷马基因的缺失对正常MPTPPPPPPPPPPPPPPPPEREADEADEADEADEADEADEADEADEREATEAD PARKISED PARKINSON pARKINSON的I型甲虫谷氨酸组I组的表达和突触前定位具有重大影响。 （2）使用大鼠脑切片中的体外贴片夹记录技术，我们证明了Globus Pallidus I组MGLURS的功能和药理特性高度依赖多巴胺能的传播，这表明这些受体在帕金森氏病中的显着功能变化。 （3）与意大利的Pisani及其同事合作，我们在大鼠Striatum中含有parvalbumin的中间神经元中表明了两组I MGlurs（mglur1a和mglur5）的共同定位。令人惊讶的是，尽管存在如此高度的共存，但体外贴片夹记录表明，MGLUR1的激活仅对这些中间神经元的膜极化具有显着的生理影响。这些数据突出了这些受体在基底神经节中的复杂性和多种作用。总之，我们的发现提供了有关基底神经节中I组的定位，功能和可塑性的重要信息，这是帕金森氏病药物治疗的新颖有希望的新型靶标。