Brazhnik Elena, McCoy Alex J, Novikov Nikolay, Hatch Christina E, Walters Judith R
Neurophysiological Pharmacology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-3702.
Neurophysiological Pharmacology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-3702
J Neurosci. 2016 Apr 13;36(15):4196-208. doi: 10.1523/JNEUROSCI.3582-15.2016.
Loss of dopamine is associated with increased synchronization and oscillatory activity in the subthalamic nucleus and basal ganglia (BG) output nuclei in both Parkinson's disease (PD) patients and animal models of PD. We have previously observed substantial increases in spectral power in the 25-40 Hz range in LFPs recorded in the substantia nigra pars reticulata (SNpr) and motor cortex (MCx) in the hemiparkinsonian rat during treadmill walking. The current study explores the hypothesis that SNpr output entrains activity in the ventral medial thalamus (VM) in this frequency range after loss of dopamine, which in turn contributes to entrainment of the MCx and BG. Electrode bundles were implanted in MCx, SNpr, and VM of rats with unilateral dopamine cell lesions. Spiking and LFP activity were recorded during epochs of rest and walking on a circular treadmill. After dopamine cell lesion, 30-36 Hz LFP activity in the VM became more robust during treadmill walking and more coherent with LFP activity in the same range in MCx and SNpr. Infusion of the GABAA antagonist picrotoxin into the VM reduced both high beta power in MCx and SNpr and coherence between MCx and SNpr while temporarily restoring walking ability. Infusion of the GABAA agonist muscimol into the VM also reduced MCx-SNpr coherence and beta power but failed to improve walking. These results support the view that synchronized neuronal activity in the VM contributes to the emergence of high beta oscillations throughout the BG-thalamocortical network in the behaving parkinsonian rat.
Parkinson's disease symptoms are associated with dramatic increases in synchronized beta range (15-35 Hz) oscillatory local field activity in several brain areas involved in motor control, but the mechanisms promoting this activity and its functional significance remain unresolved. This oscillatory activity can be recorded in awake behaving rats with unilateral dopamine cell lesions using chronically implanted electrodes. Although these rats have motor deficits, they can walk on a circular treadmill in the direction ipsilateral to their lesion. This study establishes a critical role for the ventral medial thalamus in the propagation of this exaggerated beta range oscillatory activity and the sequential entrainment of structures throughout the basal ganglia-thalamocortical loop in the lesioned hemisphere of hemiparkinsonian rats during treadmill walking.
在帕金森病（PD）患者和PD动物模型中，多巴胺缺失与丘脑底核和基底神经节（BG）输出核团的同步化增加及振荡活动增强有关。我们之前观察到，在半侧帕金森病大鼠跑步机行走过程中，黑质网状部（SNpr）和运动皮层（MCx）记录的局部场电位（LFP）在25 - 40Hz范围内的频谱功率大幅增加。本研究探讨了这样一种假说，即多巴胺缺失后，SNpr输出在该频率范围内带动腹内侧丘脑（VM）的活动，进而促成MCx和BG的带动。将电极束植入单侧多巴胺细胞损伤大鼠的MCx、SNpr和VM。在休息和在圆形跑步机上行走的时间段记录放电和LFP活动。多巴胺细胞损伤后，VM中30 - 36Hz的LFP活动在跑步机行走期间变得更强健，并且与MCx和SNpr中相同频率范围内的LFP活动更具相关性。向VM内注入GABAA拮抗剂荷包牡丹碱可降低MCx和SNpr中的高β功率以及MCx和SNpr之间的相关性，同时暂时恢复行走能力。向VM内注入GABAA激动剂蝇蕈醇也降低了MCx - SNpr相关性和β功率，但未能改善行走。这些结果支持这样一种观点，即VM中同步的神经元活动促成了行为学上帕金森病大鼠整个BG - 丘脑皮质网络中高β振荡的出现。
帕金森病症状与参与运动控制的几个脑区同步β频段（15 - 35Hz）振荡局部场活动的显著增加有关，但促进这种活动的机制及其功能意义仍未解决。使用长期植入电极可在清醒行为的单侧多巴胺细胞损伤大鼠中记录到这种振荡活动。尽管这些大鼠存在运动缺陷，但它们可以在与其损伤同侧的方向在圆形跑步机上行走。本研究确立了腹内侧丘脑在这种夸张的β频段振荡活动的传播以及半侧帕金森病大鼠损伤半球在跑步机行走期间整个基底神经节 - 丘脑皮质环路结构的顺序带动中的关键作用。
