Muralidharan A, Jensen A L, Connolly A, Hendrix C M, Johnson M D, Baker K B, Vitek J L
Department of Neurology, University of Minnesota, Minneapolis, MN 55455, United States.
Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, United States.
Exp Neurol. 2016 May;279:187-196. doi: 10.1016/j.expneurol.2016.03.002. Epub 2016 Mar 2.
Neurophysiological changes in the basal ganglia thalamo-cortical circuit associated with the development of parkinsonian motor signs remain poorly understood. Theoretical models have ranged from those emphasizing changes in mean discharge rate to increased oscillatory activity within the beta range. The present study characterized neuronal activity within and across the internal and external segments of the globus pallidus as a function of motor severity using a staged, progressively severe 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinsonism in three rhesus monkeys. An increase in coherence between neuronal pairs across the external and internal globus pallidus was present in multiple frequency bands in the parkinsonian state; both the peak frequency of oscillatory coherence and the variability were reduced in the parkinsonian state. The incidence of 8-20Hz oscillatory activity in the internal globus pallidus increased with the progression of the disease when pooling the data across the three animals; however it did not correlate with motor severity when assessed individually and increased progressively in only one of three animals. No systematic relationship between mean discharge rates or the incidence or structure of bursting activity and motor severity was observed. These data suggest that exaggerated coupling across pallidal segments contribute to the development of the parkinsonian state by inducing an exaggerated level of synchrony and loss of focusing within the basal ganglia. These data further point to the lack of a defined relationship between rate changes, the mere presence of oscillatory activity in the beta range and bursting activity in the basal ganglia to the motor signs of Parkinson's disease.
与帕金森氏症运动症状发展相关的基底神经节丘脑 - 皮质回路中的神经生理变化仍知之甚少。理论模型的范围从强调平均放电率变化的模型到强调β范围内振荡活动增加的模型。本研究使用三只恒河猴的分期、逐渐严重的1-甲基-4-苯基-1,2,3,6-四氢吡啶帕金森病模型，将苍白球内、外节内及之间的神经元活动表征为运动严重程度的函数。在帕金森病状态下，多个频段内苍白球外节和内节之间的神经元对之间的相干性增加；帕金森病状态下振荡相干的峰值频率和变异性均降低。当汇总三只动物的数据时，苍白球内节8 - 20Hz振荡活动的发生率随疾病进展而增加；然而，单独评估时它与运动严重程度无关，且仅在三只动物中的一只中逐渐增加。未观察到平均放电率、爆发活动的发生率或结构与运动严重程度之间的系统关系。这些数据表明，苍白球节段间过度耦合通过在基底神经节内诱导过度的同步水平和聚焦丧失，促成了帕金森病状态的发展。这些数据进一步表明，基底神经节中放电率变化、β范围内振荡活动的单纯存在以及爆发活动与帕金森病运动症状之间缺乏明确的关系。
