HETEROGENEITY OF SYNAPTIC NMDA RECEPTORS

我现在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所起的作用 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，与大多数大脑相关 功能和神经精神障碍的发病机制。我是 NMDA受体(NMDAR)亚单位假设的研究 构成突触后受体-通道复合体的主要作用是 突触强度的决定因素。这项工作一直是我的基础 过去8年作为计划成员提供的研究资金支持 我主要负责的兴奋性氨基酸受体项目 其中一个项目的调查员。在过去的五年里，我的研究 基于此，Endeavor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计划项目的组成部分 刚刚审查过的用于竞争续订的独立R01 并获得了资金中的百分位数排名(9.6%) 射程。尽管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， 新的奖项将允许个人在几个层面上成长。这个 更多的时间会让我更好地理解 兴奋性NMDA受体分子形态的异质性 Synapse及其翻译后修饰是 兴奋性氨基酸介导突触的NMDA成分的作用 传递，进而突触的可塑性。功能多样性 突触和突触外NMDAR在不同神经元群体中的表达 脑片和原代培养将用电子显微镜观察 生理学、解剖学和药理学技术。初步 结果提示亚基异质性和翻译后的作用 突触NMDA电流产生不同动力学的修饰 在大脑皮层神经元。将使用试验性策略来规范 不同NMDAR亚型神经元的功能和表达导致 了解神经元活性、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我们能够理解 中枢神经系统突触可塑性的分子决定因素 可能与了解神经精神障碍有关。

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.