Temel Yasin, Visser-Vandewalle Veerle, Aendekerk Brenda, Rutten Bart, Tan Sonny, Scholtissen Bart, Schmitz Christoph, Blokland Arjan, Steinbusch Harry W M
Department of Psychiatry and Neuropsychology, Division Cellular Neurosciences, European Graduate School of Neuroscience (EURON), The Netherlands.
Exp Neurol. 2005 May;193(1):43-52. doi: 10.1016/j.expneurol.2004.12.025.
The subthalamic nucleus (STN) is involved in motor and cognitive performance through its key role in the basal ganglia-thalamocortical circuits, but how these different modalities (motor and cognition) are controlled (similar vs. dissimilar) has not yet been elucidated. In the present study, the effects of bilateral STN deep brain stimulation (DBS) on motor and cognitive performance were investigated in a rat model of Parkinson disease (PD). After being trained in a choice reaction time (CRT) task, rats received bilateral injections of 6-hydroxydopamine (6-OHDA) into the striatum. One group of 6-OHDA animals was implanted bilaterally with stimulation electrodes at the level of the STN. Stimulations were performed at 130 Hz (frequency), 60 micros (pulse width), and varying amplitudes of 1, 3, 30, and 150 microA during the CRT task. Finally, rats were sacrificed and the brains processed for staining to determine the dopaminergic lesion (TH immunohistochemistry) and localization of the electrode tip (HE histochemistry). Bilateral 6-OHDA infusion significantly decreased (70%) the number of dopaminergic cells in the substantia nigra pars compacta (SNc) and increased motor time (MT), proportion of premature responding (PR), and reaction time (RT). Bilateral STN stimulation with an amplitude of 3 microA normalized 6-OHDA-induced deficits in PR and RT. Simulation with an amplitude of 30 microA reversed the lesion-induced deficits in MT and RT. Our data show for the first time that bilateral STN stimulation differentially affected the 6-OHDA-induced motor and cognitive deficits. This means that basal ganglia-thalamocortical motor and associative circuits responsible for specific motor and cognitive performance, which are processed through the STN, have unique physiological properties that can acutely and separately be modulated by specific electrical stimuli.
丘脑底核（STN）通过其在基底神经节 - 丘脑皮质回路中的关键作用参与运动和认知功能，但这些不同模式（运动和认知）是如何被控制的（相似还是不同）尚未阐明。在本研究中，在帕金森病（PD）大鼠模型中研究了双侧STN深部脑刺激（DBS）对运动和认知功能的影响。在选择反应时（CRT）任务中训练后，大鼠双侧纹状体内注射6 - 羟基多巴胺（6 - OHDA）。一组6 - OHDA处理的动物双侧植入STN水平的刺激电极。在CRT任务期间，以130Hz（频率）、60微秒（脉冲宽度）以及1、3、30和150微安的不同幅度进行刺激。最后，处死大鼠并对大脑进行染色处理，以确定多巴胺能损伤（TH免疫组织化学）和电极尖端的定位（HE组织化学）。双侧6 - OHDA注入显著减少了黑质致密部（SNc）中多巴胺能细胞的数量（70%），并增加了运动时间（MT）、过早反应比例（PR）和反应时间（RT）。3微安幅度的双侧STN刺激使6 - OHDA诱导的PR和RT缺陷恢复正常。30微安幅度的刺激逆转了损伤诱导的MT和RT缺陷。我们的数据首次表明双侧STN刺激对6 - OHDA诱导的运动和认知缺陷有不同影响。这意味着负责特定运动和认知功能的基底神经节 - 丘脑皮质运动和联合回路，通过STN进行处理，具有独特的生理特性，可被特定电刺激急性且分别调节。
