Schwab Bettina C, Heida Tjitske, Zhao Yan, van Gils Stephan A, van Wezel Richard J A
Applied Analysis, MIRA Institute of Technical Medicine and Biomedical Technology, University of Twente, Enschede, The Netherlands; Biomedical Signals and Systems, MIRA Institute of Technical Medicine and Biomedical Technology, University of Twente, Enschede, The Netherlands.
Mov Disord. 2014 Oct;29(12):1486-94. doi: 10.1002/mds.25987. Epub 2014 Aug 13.
Although increased synchrony of the neural activity in the basal ganglia may underlie the motor deficiencies exhibited in Parkinson's disease (PD), how this synchrony arises, propagates through the basal ganglia, and changes under dopamine replacement remains unknown. Gap junctions could play a major role in modifying this synchrony, because they show functional plasticity under the influence of dopamine and after neural injury. In this study, confocal imaging was used to detect connexin-36, the major neural gap junction protein, in postmortem tissues of PD patients and control subjects in the putamen, subthalamic nucleus (STN), and external and internal globus pallidus (GPe and GPi, respectively). Moreover, we quantified how gap junctions affect synchrony in an existing computational model of the basal ganglia. We detected connexin-36 in the human putamen, GPe, and GPi, but not in the STN. Furthermore, we found that the number of connexin-36 spots in PD tissues increased by 50% in the putamen, 43% in the GPe, and 109% in the GPi compared with controls. In the computational model, gap junctions in the GPe and GPi strongly influenced synchrony. The basal ganglia became especially susceptible to synchronize with input from the cortex when gap junctions were numerous and high in conductance. In conclusion, connexin-36 expression in the human GPe and GPi suggests that gap junctional coupling exists within these nuclei. In PD, neural injury and dopamine depletion could increase this coupling. Therefore, we propose that gap junctions act as a powerful modulator of synchrony in the basal ganglia.
尽管基底神经节神经活动同步性增加可能是帕金森病（PD）运动功能缺陷的基础，但这种同步性如何产生、在基底神经节中传播以及在多巴胺替代治疗下如何变化仍不清楚。缝隙连接可能在调节这种同步性中起主要作用，因为它们在多巴胺影响下和神经损伤后表现出功能可塑性。在本研究中，使用共聚焦成像检测PD患者和对照受试者尸检组织中壳核、丘脑底核（STN）以及外侧和内侧苍白球（分别为GPe和GPi）中的主要神经缝隙连接蛋白连接蛋白36。此外，我们在现有的基底神经节计算模型中量化了缝隙连接如何影响同步性。我们在人类壳核、GPe和GPi中检测到连接蛋白36，但在STN中未检测到。此外，我们发现与对照组相比，PD组织中壳核连接蛋白36斑点数量增加了50%，GPe中增加了4%，GPi中增加了109%。在计算模型中，GPe和GPi中的缝隙连接强烈影响同步性。当缝隙连接数量众多且电导较高时，基底神经节特别容易与来自皮层的输入同步。总之，人类GPe和GPi中连接蛋白36的表达表明这些核内存在缝隙连接耦合。在PD中，神经损伤和多巴胺耗竭可能会增加这种耦合。因此，我们提出缝隙连接是基底神经节同步性的有力调节因子。
