Global Dysrhythmia of Cerebro-Basal Ganglia-Cerebellar Networks Underlies Motor Tics following Striatal Disinhibition
Global Dysrhythmia of Cerebro-Basal Ganglia-Cerebellar Networks Underlies Motor Tics following Striatal Disinhibition
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DOI：
10.1523/jneurosci.4018-12.2013
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发表时间：
2013-01-09
影响因子：
5.3
通讯作者：
Isoda, Masaki
中科院分区：
文献类型：
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作者：
McCairn, Kevin W.;Iriki, Atsushi;Isoda, Masaki
运动抽搐是抽动症(TS)的主要症状，被认为是由大脑-基底节环路的异常引起的。然而，先前对TS的非侵入性神经成像已经发现小脑有很强的激活作用。到目前为止，小脑激活的电生理特性及其在基底节介导的TIC表达中的作用尚不清楚。我们使用运动性抽搐/痉挛的药理学猴子模型，对小脑、基底节和初级运动皮质的单单位活动和局部场电位进行了多点、多电极记录。在感觉运动壳核内微量注射荷包牡丹碱后，周期性抽动主要发生在口面部，相当数量的小脑神经元表现出与抽动有关的活动的相变。记录的小脑皮质神经元活动增加，85%的齿状核神经元表现出兴奋性、抑制性或多相反应。关键的是，小脑皮质神经元和兴奋型齿状神经元的异常放电大多先于行为抽动发作，表明它们是中枢起源。小脑和初级运动皮质的病理活动潜伏期基本重叠，这表明异常信号可能从基底节沿着不同的路径传递到这些结构。此外，抽动动作的发生与小脑和初级运动皮质的局部场电位棘波关系最为密切，这意味着这些结构可能起到释放明显抽动动作的门的作用。这些发现表明，基底节介导的抽动障碍的抽动产生网络超出了经典的大脑-基底节环路，导致包括小脑环路在内的全球网络节律失常。
Motor tics, a cardinal symptom of Tourette syndrome (TS), are hypothesized to arise from abnormalities within cerebro-basal ganglia circuits. Yet noninvasive neuroimaging of TS has previously identified robust activation in the cerebellum. To date, electrophysiological properties of cerebellar activation and its role in basal ganglia-mediated tic expression remain unknown. We performed multisite, multielectrode recordings of single-unit activity and local field potentials from the cerebellum, basal ganglia, and primary motor cortex using a pharmacologic monkey model of motor tics/TS. Following microinjections of bicuculline into the sensorimotor putamen, periodic tics occurred predominantly in the orofacial region, and a sizable number of cerebellar neurons showed phasic changes in activity associated with tic episodes. Specifically, 64% of the recorded cerebellar cortex neurons exhibited increases in activity, and 85% of the dentate nucleus neurons displayed excitatory, inhibitory, or multiphasic responses. Critically, abnormal discharges of cerebellar cortex neurons and excitatory-type dentate neurons mostly preceded behavioral tic onset, indicating their central origins. Latencies of pathological activity in the cerebellum and primary motor cortex substantially overlapped, suggesting that aberrant signals may be traveling along divergent pathways to these structures from the basal ganglia. Furthermore, the occurrence of tic movement was most closely associated with local field potential spikes in the cerebellum and primary motor cortex, implying that these structures may function as a gate to release overt tic movements. These findings indicate that tic-generating networks in basal ganglia mediated tic disorders extend beyond classical cerebro-basal ganglia circuits, leading to global network dysrhythmia including cerebellar circuits.