Behavioural disorders induced by external globus pallidus dysfunction in primates -: II.: Anatomical study
Behavioural disorders induced by external globus pallidus dysfunction in primates -: II.: Anatomical study
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DOI：
10.1093/brain/awh239
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发表时间：
2004-09-01
期刊：
影响因子：
14.5
通讯作者：
Tremblay, L
中科院分区：
文献类型：
--
作者：
François, C;Grabli, D;Tremblay, L
基底神经节的解剖组织支持它们参与运动和行为障碍。因此，运动障碍，注意力缺陷伴或不伴多动症，刻板行为，可以通过微量注射荷包牡丹碱，GABA能拮抗剂，到不同部位的外部苍白球（GPe）的猴子。本研究的目的是确定基底神经节内的解剖功能回路，这些回路与这些行为变化中的每一个都特别相关。为此，轴突示踪剂注射在相同的苍白球的网站，异常行为已经获得了荷包牡丹碱显微注射。标记映射在不同的基底神经节，并与地形的皮质-striatopallidal预测已经在文献中报道，并与钙结合蛋白免疫反应性的分布相匹配。我们的研究结果首先表明，苍白球的网站相关的运动障碍，注意力缺陷或不多动，刻板的行为，分别在电机，联想和边缘的领土，定义为弱，中度和密集的钙结合蛋白免疫反应。在这些不同的苍白球部位和解剖功能区域进行示踪剂注射后，在不同基底神经节中的标记分布之间观察到相同的关系。因此，关于纹状体内回路的起源，在运动障碍部位进行的示踪剂注射标记了位于后感觉运动壳核中的神经元，在活动过度和/或注意力缺陷中进行的示踪剂注射标记了外侧背壳核和尾状核中的神经元，对应于联合和前运动区的区域，而那些在刻板行为部位进行的实验则标记了腹侧边缘纹状体的神经元。关于基底神经节上的GPe输出，即使存在部分重叠，不同的回路也出现了不同的解剖功能区域。这些解剖电路系统地涉及内部苍白球（GPi）和黑质网状部（SNr），但运动电路主要与GPi有关，刻板行为主要与SNr有关。此外，丘脑底核的亚区域也系统地参与，这取决于所产生的运动或行为障碍。这些结果表明，不同的电路，涉及不同的解剖功能领域的基底神经节，部分重叠，参与不同的行为障碍的猴子。这些神经元回路似乎与抽动秽语综合征、注意力缺陷/多动障碍和强迫症等病理有关。本研究从治疗学角度为进一步研究提供了基础。
The anatomical organization of the basal ganglia supports their involvement in movement and behavioural disorders. Thus dyskinesia, attention deficit with or without hyperactivity, and stereotyped behaviour can be induced by microinjections of bicuculline, a GABAergic antagonist, into different parts of the external globus pallidus (GPe) in monkeys. The aim of the present study was to determine the anatomo-functional circuits inside the basal ganglia which are specifically related to each of these behavioural changes. For that, axonal tracers were injected in the same pallidal sites where abnormal behaviours have previously been obtained by bicuculline microinjections. The labelling was mapped in the different basal ganglia and matched with the topography of the cortico-striatopallidal projections already reported in the literature and with the distribution of calbindin immunoreactivity. Our results first show that the pallidal sites related to dyskinesia, attention deficit with or without hyperactivity, and stereotyped behaviour, were respectively in motor, associative and limbic territories, defined as weak, moderate and intensive calbindin immunoreactivity. The same relationship was observed between the distribution of the labelling in the different basal ganglia after tracer injections performed in these different pallidal sites and the anatomo-functional territories. Thus regarding the origin of the circuits within the striatum, tracer injections performed in the dyskinesia site labelled neurons located in the posterior sensorimotor putamen, those performed in the hyperactivity and/or attention deficit labelled neurons in the laterodorsal putamen and caudate nucleus, regions corresponding to associative and anterior motor territories, while those performed in the stereotyped behaviour site labelled neurons in the ventral limbic striatum. Regarding the GPe output on the basal ganglia, the different circuits also appeared underlined by different anatomo-functional territories, even if a partial overlap exists. Each of these anatomical circuits systematically involves both the internal globus pallidus (GPi) and the substantia nigra pars reticulata (SNr) but, whereas movement circuit is mainly related to the GPi, stereotyped behaviour is mainly related to the SNr. Additionally, subregions of the subthalamic nucleus were also systematically involved, depending on the movement or behavioural disorder produced. These results demonstrate that distinct circuits involving different anatomo-functional territories of the basal ganglia, with partial overlap, participate in different behavioural disorders in monkeys. It seems likely that these neuronal circuits are involved in pathologies like Tourette's syndrome, attention deficit/hyperactivity disorders and obsessional compulsive troubles. This study provides the basis for further researches with a therapeutical viewpoint.