HETEROGENEITY OF SYNAPTIC NMDA RECEPTORS

突触 NMDA 受体的异质性

• 批准号: 2745692
• 负责人: Stefano Vicini
• 金额: $ 7.74万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-15 至 2003-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2745692
• 关键词: NMDA receptors; excitatory aminoacid; laboratory rat; neural transmission; neurotrophic factors; posttranslational modifications; protein isoforms; protein structure function; receptor expression; synapses; tissue /cell culture

I am currently an Associate Professor in the Department of Physiology at Georgetown University. My long term research goal is to understand the role of the large heterogeneity of molecular forms of amino acid receptors as determinant of the strength and of long-term modifications of synapses in the central nervous system, relevant to most brain function and to the pathogenesis of neuropsychiatric disorders. I am investigating the hypotheses that NMDA receptor (NMDAR) subunits composing postsynaptic receptor-channel complexes play a major role as determinants of synaptic strength. This work has been the basis for my research funding support for the last 8 years as a member of a Program Project on excitatory amino acid receptors of which I was principal investigator of one of the project. For the last five years my research endeavor was also supported by a RCDA award from the NINDS based on that project. I recently resubmitted my component of the program project as an independent R01 for competitive renewal that has just been reviewed and received a percentile ranking (9.6 percent) within the funding range. Although this support was essential to my development I still feel that by minimizing my teaching and administrative responsibilities, the new award will allow for personal growth at several levels. The additional time will permit me to gain strengths in understanding how the heterogeneity of molecular forms of NMDA receptor at excitatory synapse and their posttranslational modifications underlie the effectiveness of the NMDA component of EAA mediated synaptic transmission and in turn synaptic plasticity. The functional diversity of synaptic and extrasynaptic NMDAR in distinct neuronal populations in brain slices and primary culture will be investigated with electro- physiological, anatomical and pharmacological techniques. Preliminary results suggest roles for subunit heterogeneity and posttranslational modifications in producing distinct kinetics of synaptic NMDA currents in cortical neurons. Experimental strategies will be used to regulate function and expression of distinct NMDAR subtypes neurons resulting in the understanding of how neuronal activity, protein kinases and neurotrophins controls the expression of NMDA receptor subtypes. Data obtained from these specific aims will permit the understanding of the molecular determinant responsible for synaptic plasticity in CNS possibly relevant o for the understanding of neuropsychiatric disorders.

我目前是生理学系的副教授 在乔治城大学 我的长期研究目标是了解 氨基酸分子形式的巨大异质性 受体作为强度和长期修饰的决定因素 中枢神经系统中的突触，与大多数大脑 功能和神经精神疾病的发病机制。 我是 研究NMDA受体亚单位 组成突触后受体通道复合物起主要作用， 突触强度的决定因素。 这项工作一直是我的基础， 作为项目成员，过去8年的研究资金支持 兴奋性氨基酸受体项目，我是该项目的负责人 一个项目的调查员。 在过去的五年里， 奋进也得到了NINDS颁发的RCDA奖的支持， 项目 我最近重新提交了我的程序项目的组成部分， 一个独立的R 01，用于竞争性续约，刚刚经过审查 并在资助范围内获得了百分位排名（9.6%）， 范围虽然这种支持对我的发展至关重要，但我仍然 我觉得通过减少我的教学和行政责任， 新的奖项将允许在几个层次上的个人成长。 的 额外的时间将使我能够在理解如何 NMDA受体分子形式的异质性 突触及其翻译后修饰是 NMDA成分对EAA介导的突触 传递和突触可塑性。 功能多样性 突触和突触外NMDAR在不同的神经元群体， 脑切片和原代培养将用电- 生理学、解剖学和药理学技术。初步 结果表明亚基异质性和翻译后 在产生突触NMDA电流的不同动力学中的修饰 大脑皮层神经元 实验策略将用于调节 不同NMDAR亚型神经元的功能和表达， 了解神经元活动、蛋白激酶和 神经营养因子控制NMDA受体亚型的表达。 数据 从这些具体目标中获得的信息将使人们能够理解 负责中枢神经系统突触可塑性的分子决定因素 可能与理解神经精神疾病有关。