Department of Neurosurgery, Hannover Medical School, 30625 Hannover, Germany.
J Comp Neurol. 2013 Oct 1;521(14):3226-40. doi: 10.1002/cne.23342.
Lesions of the rat nigrostriatal dopamine system by injection of 6-hydroxydopamine (6-OHDA) lead to abnormal neuronal activity in the basal ganglia (BG) motor loop similar to that found in Parkinson's disease (PD). In the BG motor loop the subthalamic nucleus (STN) represents an important structure, which, however, also comprises areas of the BG associative and limbic loops. We were interested whether neuronal activity would differ between the STN medial associative-limbic and lateral motor part, and whether selective 6-OHDA-induced lesions of the dorsolateral striatum, the entrance region of the BG motor loop, would differently affect these subregions. In male Sprague-Dawley rats 6-OHDA (n = 12) or vehicle (n = 10) was bilaterally injected in the dorsolateral striatum. Four weeks later extracellular single-unit activity and local field potentials were recorded in medial and lateral STN neurons of urethane-anesthetized rats. In sham-lesioned rats the discharge rate and burst activity were higher in the lateral compared to the medial STN. Similar differences were found for other neuronal activity measures (coefficient of variation of interspike interval, skewness, kurtosis, approximate entropy). After 6-OHDA injection neuronal burst activity was enhanced, while the discharge rate was not affected. In addition, in 6-OHDA-lesioned rats β-band oscillatory activity was enhanced, with no difference between STN subregions. We found important differences of neuronal activity between STN subregions, indicating functional segregation. However, selective 6-OHDA lesions of the dorsolateral striatum also had a pronounced effect on the medial STN subregion, indicating interaction between BG loops.
6-羟多巴胺(6-OHDA)注射损伤大鼠黑质纹状体多巴胺系统,导致基底神经节(BG)运动回路中的异常神经元活动,类似于帕金森病(PD)中发现的活动。在 BG 运动回路中,丘脑底核(STN)是一个重要的结构,但它也包含 BG 联合和边缘回路的区域。我们感兴趣的是 STN 内侧联合-边缘和外侧运动部分的神经元活动是否不同,以及选择性 6-OHDA 诱导的外侧纹状体(BG 运动回路的入口区域)损伤是否会对这些亚区产生不同的影响。在雄性 Sprague-Dawley 大鼠中,将 6-OHDA(n = 12)或载体(n = 10)双侧注射到外侧纹状体中。四周后,在麻醉的 urethane 大鼠的内侧和外侧 STN 神经元中记录细胞外单单位活动和局部场电位。在 sham-lesioned 大鼠中,与内侧 STN 相比,外侧 STN 的放电率和爆发活动更高。对于其他神经元活动测量值(尖峰间间隔的变异系数、偏度、峰度、近似熵)也发现了类似的差异。在 6-OHDA 注射后,神经元爆发活动增强,而放电率不受影响。此外,在 6-OHDA 损伤大鼠中,β 波段振荡活动增强,STN 亚区之间没有差异。我们发现 STN 亚区之间的神经元活动存在重要差异,表明功能分离。然而,外侧纹状体的选择性 6-OHDA 损伤对内侧 STN 亚区也有明显影响,表明 BG 回路之间存在相互作用。