UMR INSERM U930, Université François Rabelais de Tours, Tours, France.
AP-HP, Department of Nuclear Medicine, Pitié-Salpêtrière Hospital, Sorbonne University, UPMC Paris 06, CNRS UMR 7371, INSERM U1146, 75013 Paris, France.
Neuroimage. 2017 Feb 1;146:1025-1037. doi: 10.1016/j.neuroimage.2016.10.039. Epub 2016 Oct 29.
The external pallidum (GPe) is a component of the indirect pathway centrally placed in the basal ganglia. Studies already demonstrated that the pharmacological disinhibition of the sensorimotor, associative, and limbic GPe produced dyskinesia, hyperactivity, and compulsive behaviors, respectively. The aim of this study was to investigate the cortical regions altered by the disinhibition of each GPe functional territory. Thus, 5 macaques were injected with bicuculline in sensorimotor, associative, and limbic sites of the GPe producing dyskinesia, hyperactivity, and compulsive behaviors, and underwent in vivo positron tomography with F-2-fluoro-2-deoxy-D-glucose to identify cortical dysfunctions related to GPe disinhibition. Blood cortisol levels were also quantified as a biomarker of anxiety for each condition. Our results showed that pallidal bicuculline injections in anesthetized animals reproducibly modified the activity of specific ipsilateral and contralateral cortical areas depending on the pallidal territory targeted. Bicuculline injections in the limbic GPe led to increased ipsilateral activations in limbic cortical regions (anterior insula, amygdala, and hippocampus). Injections in the associative vs. sensorimotor GPe increased the activity in the ipsilateral midcingulate vs. somatosensory and parietal cortices. Moreover, bicuculline injections increased blood cortisol levels only in animals injected in their limbic GPe. These are the first functional results supporting the model of opened cortico-striato-thalamo-cortical loops where modifications in a functional pallidal territory can impact cortical activities of the same functional territory but also cortical activities of other functional territories. This highlights the importance of the GPe as a crucial node in the top-down control of the cortico-striato-thalamo-cortical circuits from the frontal cortex to influence the perception, attention, and emotional processes at downstream (or non-frontal) cortical levels. Finally, we showed the implication of the ventral pallidum with the amygdala and the insular cortex in a circuit related to aversive processing that should be crucial for the production of anxious disorders.
苍白球外部（GPe）是基底神经节中位于中央的间接通路的组成部分。已有研究表明，感觉运动、联合和边缘 GPe 的药理学去抑制分别导致运动障碍、多动和强迫行为。本研究旨在探讨 GPe 每个功能区域去抑制所改变的皮质区域。因此，将 5 只猕猴的 GPe 感觉运动、联合和边缘部位注射荷包牡丹碱，产生运动障碍、多动和强迫行为，并进行 F-2-氟-2-脱氧-D-葡萄糖的体内正电子断层扫描，以确定与 GPe 去抑制相关的皮质功能障碍。还对每种情况下的皮质醇水平进行了量化，作为焦虑的生物标志物。我们的结果表明，在麻醉动物中，苍白球内注射荷包牡丹碱可根据目标苍白球区域有规律地改变特定同侧和对侧皮质区域的活动。在边缘 GPe 中注射荷包牡丹碱导致边缘皮质区域（前岛叶、杏仁核和海马体）的同侧激活增加。与感觉运动 GPe 相比，在联合 GPe 中的注射增加了同侧中扣带回皮质相对于体感和顶叶皮质的活动。此外，只有在注射到边缘 GPe 的动物中，荷包牡丹碱注射才会增加皮质醇水平。这些是第一个支持开放皮质纹状体丘脑皮质回路模型的功能结果，其中功能苍白球区域的改变可以影响同一功能区域的皮质活动，也可以影响其他功能区域的皮质活动。这突出了 GPe 作为从额叶皮质到下游（或非额叶）皮质水平影响感知、注意力和情绪过程的皮质纹状体丘脑皮质回路的自上而下控制的关键节点的重要性。最后，我们展示了腹侧苍白球与杏仁核和岛叶皮质在与厌恶处理相关的回路中的作用，这对产生焦虑障碍至关重要。
