D1 AND D5 RECEPTOR SIGNALING IN MONKEY PFC

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本项目的目的是使用电子显微镜技术来确定灵长类动物前额叶皮层内D1和D5多巴胺受体及其信号蛋白的定位，并利用免疫沉淀方法确定这些受体及其下游效应蛋白之间的任何物理相互作用。 前额叶皮层有一个复杂的回路，了解这两个受体在这个回路的特定元件中的位置将加深我们对D1家族受体信号传导如何影响前额叶功能的理解。 我们以前已经确定了D1和D5在前额叶皮层（PFC）神经元的第一，第三和第五层的本地化;确定了他们的共同定位在树突棘和轴突终末的第三层;并确定D1和D5定位到小白蛋白和钙视网膜蛋白interneuron树突和轴突终末。 在本报告所述期间，我们确定了两个D1和D5信号蛋白，DARPP-32和抑制剂-1，在灵长类PFC的第三层的neuronal定位;确定了它们在树突棘和轴突终末内的定位;并确定了它们在小白蛋白和钙网膜中间神经元的定位。 我们还确定了两个蛋白磷酸酶-1（PP 1）亚型的定位，以小白蛋白和钙视网膜蛋白interneurons，并比较了所有感兴趣的蛋白质（D1，D5，DARPP-32，I-1，和PP 1亚型）的神经元和interneurons的定位，以获得每种类型的神经元隔室的个别信号转导环境。

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. The purpose of this project has been to use electron microscopic techniques to determine the localization of the D1 and D5 dopamine receptors and their signaling proteins within primate prefrontal cortex, and identify any physical interactions between these receptors and their downstream effector proteins utilizing immunoprecipitation methods. The prefrontal cortex has a complicated circuitry, and understanding where these two receptors are located within specific elements of this circuitry will deepen our understanding of how D1 family receptor signaling effects prefrontal functioning. We have previously determined the localization of D1 and D5 in prefrontal cortex (PFC) neuropil of layers I, III and V; determined their co-localization within dendritic spines and axon terminals of layer III; and determined D1 and D5 localization to parvalbumin and calretinin interneuron dendrites and axon terminals. During the reporting period, we determined the neuropil localization of two D1 and D5 signaling proteins, DARPP-32 and Inhibitor-1, in layer III of the primate PFC; determined their localization within dendritic spines and axon terminals; and determined their localization to parvalbumin and calretinin interneurons. We also determined the localization of two protein phosphatase-1 (PP1) isoforms to parvalbumin and calretinin interneurons, and have compared the neuropil and interneuron localization of all proteins of interest (D1, D5, DARPP-32, I-1, and PP1 isoforms) to derive individual signal transduction environments for each type of neuronal compartment.