Bicuculline-Induced Chorea Manifests in Focal Rather Than Globalized Abnormalities in the Activation of the External and Internal Globus Pallidus
Bicuculline-Induced Chorea Manifests in Focal Rather Than Globalized Abnormalities in the Activation of the External and Internal Globus Pallidus
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DOI：
10.1152/jn.00093.2010
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发表时间：
2010-12-01
影响因子：
2.5
通讯作者：
Bar-Gad, Izhar
中科院分区：
文献类型：
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作者：
Bronfeld, Maya;Belelovsky, Katya;Bar-Gad, Izhar
Bronfeld M，Belelovsky K，Erez Y，Bugaysen J，Korngreen A，Bar-Gad I.荷包牡丹碱诱导的舞蹈病表现为苍白球内外激活的局灶性异常，而不是球状性异常。神经生理学杂志104：3261-3275,2010。2010年6月30日首次出版；DOI：10.1152/jn.00093.2010。舞蹈症是一种与基底节(BG)相关的多动运动障碍，其特征是不规则的连续非自主运动。向苍白球(GPE)局部微量注射GABA A拮抗剂荷包牡丹碱可诱导行为灵长类动物出现舞蹈症和相关的过度行为障碍。在荷包牡丹碱微量注射前、中、后，我们在GPE和苍白球内(GPI)进行了多电极细胞外记录。荷包牡丹碱可引起GPE神经元放电频率增加和放电模式改变。在靠近荷包牡丹碱微量注射部位的GPE神经元中发现了两种异常的神经元放电模式：持续高频活动和双稳态活动，其中神经元在高频和完全停止放电之间转换。GPE和GPI内部和之间的神经元活动仍然不相关，没有证据表明局灶性GPE异常活动向GPI下游传播。尽管荷包牡丹碱影响的GPE神经元的信息能力降低，但编码行为事件的能力保持不变。我们在大鼠的体外实验中发现了GPE神经元对荷包牡丹碱的类似反应，这表明了这些异常放电模式背后的基本细胞机制。这些结果表明，舞蹈病与局灶性神经元变化有关，而BG核的整体变化没有补充这种变化。这表明BG控制的随机相变机制导致了舞蹈病的混沌性质。因此，舞蹈症可能与大脑皮层内部信息处理的变化有关，而不是施加大脑皮层兴奋性的全球化状态。
Bronfeld M, Belelovsky K, Erez Y, Bugaysen J, Korngreen A, Bar-Gad I. Bicuculline-induced chorea manifests in focal rather than globalized abnormalities in the activation of the external and internal globus pallidus. J Neurophysiol 104: 3261-3275, 2010. First published June 30, 2010; doi:10.1152/jn.00093.2010. Chorea is a basal-ganglia (BG) related hyperkinetic movement disorder characterized by irregular continuous involuntary movements. Chorea and related hyperbehavioral disorders may be induced in behaving primates by local microinjections of the GABA A antagonist bicuculline to the globus pallidus externus (GPe). We performed multielectrode extracellular recordings in the GPe and in the globus pallidus internus (GPi) before, during, and after bicuculline microinjections. Bicuculline led to an increase in the firing rate and a change in the firing pattern of GPe neurons. Two types of abnormal neuronal firing patterns were detected in GPe neurons close to the bicuculline microinjection site: continuous high-frequency activity and bistable activity, in which neurons transitioned between high-frequency and complete cessation of firing. Neuronal activity remained uncorrelated within and between the GPe and the GPi, with no evidence for propagation of the focal GPe abnormal activity downstream to the GPi. Despite reduction in the information capacity of bicuculline-affected GPe neurons, the ability to encode behavioral events was maintained. We found similar responses of GPe neurons to bicuculline in vitro in the rat, suggesting a basic cellular mechanism underlying these abnormal firing patterns. These results demonstrate that chorea is associated with focal neuronal changes that are not complemented by global changes in the BG nuclei. This suggests a mechanism of stochastic phasic alteration of BG control leading to the chaotic nature of chorea. Thus rather than imposing a globalized state of cortical excitability, chorea might be associated with changes in internal information processing within the BG.