Dopaminergic Modulation of Corticostriatal Activity

描述(申请人提供)：这项研究检测了皮质驱动的纹状体即刻早期基因(LEG)表达的多巴胺能调节。皮质去抑制诱导大鼠纹状体背外侧部分Fos的表达。以前的研究表明，多巴胺(DA)对纹状体神经元有不同的影响，因此它可能调节纹状体对皮质输入的反应。此外，虽然DA能传入基底节(BG)的主要靶点是纹状体，但BG的其他核团也接受DA能传入。苍白球(GP)是BG的一个受DA直接调制的区域，它也有向纹状体的传出投射。因此，GP是DA能调节可以影响纹状体功能的区域。其具体目的是：1)通过使用ICC双标记技术显示Fos和小白蛋白(Pv)，研究纹状体神经元亚群中皮质驱动的纹状体腿反应的模式；2)检测由于多巴胺耗竭而引起的这一模式的变化；3)使用舒必利在苍白球内应用舒必利来检测由于阻断GP中的DA受体而引起的这一模式的变化；以及4)使用奎必利来检测由于刺激GP中的DA受体而引起的这种模式的变化。通过研究DA在纹状体和GP中对皮质驱动纹状体腿反应的影响，将获得关于DA如何调节基底节功能的信息。这些信息可能为理解帕金森氏病等运动障碍的机制提供基础，并可能为治疗干预提供可能的纹状体外靶点的重要见解。

DESCRIPTION(As provided by Applicant): This research examines the dopaminergic modulation of cortically-driven striatal immediate-early gene (lEG) expression. Cortical disinhibition induces Fos expression in the dorsolateral portion of the striatum in rats. Previous research has shown that dopamine (DA) has differential effects on striatal neurons, and thus it may modulate striatal response to cortical input. In addition, although the main target of DA-ergic input to the basal ganglia (BG) is the striatum, other BG nuclei receive DA-ergic afferents. The globus pallidus (GP) is an area of the BG that is directly modulated by DA and it also has efferent projections to the striatum. Thus the GP is an area in which DA-ergic modulation can affect striatal function. The specific aims are: 1) to examine the pattern of cortically driven striatal lEG response in subpopulations of striatal neurons by using double-labeling ICC techniques to visualize Fos and parvalbumin (PV); 2) to examine changes in this pattern due to dopamine depletion; 3) to examine changes in this pattern due to blockade of DA receptors in the GP, using intrapallidal application of sulpiride; and 4) to examine changes in this pattern due to stimulation of DA receptors in the GP using inirapallidal application of quinpirole. By examining the effects of DA, both in the striatum and in the GP, on cortically driven striatal lEG response information will be gained about how DA modulates basal ganglia functioning. This information may provide a basis for understanding mechanisms involved in motor disorders such as Parkinson's disease, and may provide important insights into possible extra-striatal targets for therapeutic interventions.