Dopaminergic Modulation of Corticostriatal Activity

描述（由申请人提供）：本研究探讨了多巴胺能对皮质驱动纹状体立即早期基因（lEG）表达的调节。皮质解除抑制诱导大鼠纹状体背外侧Fos表达。先前的研究表明，多巴胺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层输入的反应。此外，虽然基底神经节（BG）的da能输入的主要目标是纹状体，但其他BG核也接受da能传入。苍白球（GP）是BG的一个直接受DA调节的区域，它也对纹状体有传出投射。因此，GP是一个区域，其中da能调节可以影响纹状体的功能。具体目的是：1)通过使用双标记ICC技术可视化Fos和小白蛋白（PV），研究纹状体神经元亚群中皮质驱动纹状体lEG反应的模式；2)检查多巴胺耗竭引起的这种模式的变化；3)通过使用舒必利，检查由于GP中DA受体的阻断而导致的这种模式的变化；4)研究喹匹罗在腹腔内应用刺激GP中的DA受体所引起的这种模式的变化。通过检查多巴胺在纹状体和GP中对皮质驱动纹状体lEG反应的影响，将获得多巴胺如何调节基底神经节功能的信息。这一信息可能为理解帕金森病等运动障碍的机制提供基础，并可能为治疗干预的纹状体外靶点提供重要见解。

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.