CORTICAL CIRCUITRY RELATED TO NEUROTRANMISSION PROTEINS

与神经传递蛋白相关的皮质回路

• 批准号: 7562515
• 负责人: Emil CHRIS MULY
• 金额: $ 3.16万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7562515
• 关键词: Antipsychotic Agents; Basal Ganglia; Complement; Complex; Computer Retrieval of Information on Scientific Projects Database; Data; Dendritic Spines; Dopamine; Dopamine D1 Receptor; Drug effect disorder; Funding; Grant; Institution; Label; Lead; Methods; Molecular; Monkeys; Neurabin; Neurons; Numbers; Population; Protein Isoforms; Proteins; Rattus; Receptor Activation; Research; Research Personnel; Resources; Schizophrenia; Short-Term Memory; Signal Transduction; Source; United States National Institutes of Health; Vertebral column; Work; neurotransmission; spinophilin

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 work relates prefrontal cortical circuitry with the molecular components of dopamine neurotransmission. The results relate to the circuitry of working memory, which is dysfunctional in schizophrenia. Working memory function depends on an optimal level of D1 receptor activation and is impaired by both over and under stimulation of D1 receptor. It is hoped that our results will lead to a better understanding of the mechanism of the D1 receptor's complex modulation of working memory, and ultimately to a better understanding of antipsychotic drug action. We have used post-embedding immunogold labeling to examine the distribution of PP1 targeting proteins (spinophilin and neurabin) and PP1(alpha) and PP1(gamma1) in spines. Our data indicates that the D1 receptor has access to different complements of signal transduction proteins in different neuronal compartments and suggests functional differences for the two PP1 isoforms. The finding that not all dendritic spines are equal, but that different populations of spines have different sets of signal transduction proteins provides new mechanisms for varying the effect of different inputs onto single neurons. Finally we have used single and pre-embedding double label methods to examine the subcellular localization of group I mGluRs (mGluR1a and mGluR5) and determined a number of differences in their distribution, both between each other, between monkey cortex and rat cortex and between cortex and basal ganglia.

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。 这项工作将前额叶皮质回路与多巴胺神经传递的分子成分有关。结果与工作记忆的电路有关，这在精神分裂症中是功能失调的。 工作记忆函数取决于D1受体激活的最佳水平，并且刺激D1受体会损害。希望我们的结果能够更好地理解D1受体对工作记忆的复杂调节的机制，并最终更好地理解抗精神病药作用。我们已经使用后填充免疫元标记来检查刺中PP1靶向蛋白（Spinophilin和Neurabin）和PP1（Alpha）和PP1（Gamma1）的分布。我们的数据表明，D1受体可以访问不同神经元室中信号转导蛋白的不同补体，并提出了两个PP1同工型的功能差异。并非所有树突状刺都相等的发现，但是不同的棘突具有不同的信号转导蛋白集，这为改变不同输入对单个神经元的影响提供了新的机制。 最后，我们已经使用了单一和预先装饰的双重标签方法来检查I组MGLURS（MGLUR1A和MGLUR5）的亚细胞定位，并确定了它们的分布差异，彼此之间，猴子皮质和大鼠皮质之间以及皮质和基础神灵之间的分布之间的分布差异。