EFFECTS OF PARTIAL LOSS OF DOPAMINE INPUTS ON PREFRONTAL CORTICAL FUNCTION

多巴胺输入部分丧失对前额皮质功能的影响

• 批准号: 6456265
• 负责人: MICHAEL J ZIGMOND
• 金额: $ 22.86万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6456265
• 关键词: axon; developmental neurobiology; disease /disorder model; dopamine; electrophoresis; experimental brain lesion; gamma aminobutyrate; high performance liquid chromatography; immunocytochemistry; in situ hybridization; interneurons; laboratory rat; neural transmission; neurochemistry; nucleus accumbens; prefrontal lobe /cortex; schizophrenia

As summarized in the Center Overview, schizophrenia appears to be associated with a reduction in the dopamine (DA) innervation of prefrontal cortex (PFC). However, the functional impact of such a deficit especially on other elements of PFC circuitry that are though to be dysfunctional schizophrenia, has not been well characterized. The proposed experiments will use a rat model and in vivo neurochemical methods to examine four questions relevant to this issue: (1) What is the impact of loss of DA axons in PFC on extracellular DA in this region? (2) What is the impact of this loss on the function of gamma-aminobutyric acid (GABA) interneurons in PFC? (3) Does loss of DA in PFC alter the ability of PFC to regulate the activity of one of its subcortical targets, the mesoaccumbens DA projection? (4) Does loss of DA axons in PFC sustained early in development produce changes in PFC function that are different from those seen in rats lesioned as adults? The neurochemical experiments described in the present project complement the studies of Projects Grace and Barrionuevo, which explore factors regulating the electrophysiological activity of PFC in rat and monkey. In addition, results of the proposed experiments will generate information about neurochemical interactions in the PFC of rat that will be used to guide the interpretation of data collected in behavioral and imaging studies in schizophrenic subjects (Projects-Cohen and Project-Sweeney), as well as to generate hypotheses regarding the neurochemical deficits of schizophrenia that may then be tested in functional imaging studies (Projects-Cohen and Sweeney) or be analysis of postmortem tissue (Project-Lewis).

正如中心概述中总结的那样，精神分裂症似乎是 与额叶的多巴胺（DA）神经支配减少有关 皮质（PFC）。但是，尤其是这种赤字的功能影响 在PFC电路的其他元素上，该元素是功能失调的 精神分裂症，尚未得到很好的特征。提出的实验 将使用大鼠模型和体内神经化学方法检查四种 与此问题相关的问题：（1）损失DA的影响是什么 该区域的细胞外DA上的PFC中的轴突？ （2） 这种对γ-氨基丁酸（GABA）中间神经元功能功能的损失 在PFC中？ （3）PFC中DA的损失会改变PFC调节的能力 中皮层靶标之一的活性是中含中的da 投影？ （4）在PFC中确实损失了DA轴突的早期 开发产生与PFC功能不同的变化 在大鼠病变中看到成年人？描述的神经化学实验 在本项目中，对项目恩典和项目的研究补充 Barrionuevo，探索调节电生理的因素 PFC在大鼠和猴子中的活性。此外，提议的结果 实验将生成有关神经化学相互作用的信息 将用于指导数据解释的大鼠PFC 在精神分裂症患者的行为和成像研究中收集 （Projects-Cohen和Project-Sweeney），以及产生假设 关于精神分裂症的神经化学缺陷，可能是 在功能成像研究（Projects-Cohen和Sweeney）中进行了测试或 分析死后组织（项目路易威普）。