EFFECTS OF PARTIAL LOSS OF DOPAMINE INPUTS ON PREFRONTAL CORTICAL FUNCTION

正如中心概述中总结的那样，精神分裂症似乎是 与前额叶多巴胺(DA)神经支配减少有关 皮层(PFC)。然而，这种赤字对功能的影响尤其是 关于PFC电路中被认为有故障的其他元件 精神分裂症，一直没有得到很好的描述。拟议中的实验 将使用老鼠模型和体内神经化学方法来检查四个 与这一问题有关的问题：(1)DA的损失有什么影响 PFC内轴突对该区域细胞外DA的影响？(2) γ-氨基丁酸(GABA)中间神经元功能的丧失 在PFC中？(3)PFC中DA的丢失是否改变了PFC的调节能力 其皮质下靶标之一--中隔伏隔核DA的活性 预测？(4)PFC中DA轴突的丢失在早期持续吗？ 发展带来了PFC功能的变化，这些变化与 在成年老鼠身上看到的吗？所描述的神经化学实验 在本项目中补充对Grace和项目的研究 Barrionuevo，探索电生理调节因素 PFC在大鼠和猴体内的活性。此外，建议的结果 实验将产生关于神经化学相互作用的信息 将用于指导数据解释的RAT的PFC 在精神分裂症受试者的行为和影像研究中收集 (项目-科恩和项目-斯威尼)，以及产生假设 关于精神分裂症的神经化学缺陷，那可能是 在功能成像研究(项目-Cohen和Sweeney)或BE中进行测试 身体组织分析(Project-Lewis)。

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).