The pharmacological blockade of medial forebrain bundle induces an acute pathological synchronization of the cortico-subthalamic nucleus-globus pallidus pathway
The pharmacological blockade of medial forebrain bundle induces an acute pathological synchronization of the cortico-subthalamic nucleus-globus pallidus pathway
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DOI：
10.1113/jphysiol.2009.172759
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发表时间：
2009-09-15
影响因子：
5.5
通讯作者：
Stefani, Alessandro
中科院分区：
文献类型：
--
作者：
Galati, Salvatore;Stanzione, Paolo;Stefani, Alessandro
帕金森病大鼠模型基底神经节（BG）不同部位放电的病理振荡特征。最近的文献集中在清醒大鼠中β频段的突出性。然而，在6-羟基多巴胺损伤的动物中，苍白球（GP）和网状黑质的放电与多巴胺诱导的皮层慢波活动同步。这种病理协同作用在低频率的神经元基础是广泛争论。为了了解黑质的作用pars黑质（SNc）信号在病理同步化的发展，我们进行了药理学失活的内侧前脑束（MFB）通过河豚毒素（TTX），这导致了一个戏剧性的，但可逆的，减少多巴胺含量在纹状体。这一过程引起了明显的对侧运动不能，麻醉消失后即可检测到，持续约3-4小时。我们试图确定这种短暂性帕金森样运动减退综合征的电生理对应物。因此，我们获得了正常大鼠MFB注射TTX前后的皮层电图（ECoG）和GP和丘脑底核（GNP）的单个单位记录。有趣的是，TTX介导的MFB失活诱导皮层和GP之间的快速发展的一致性和皮层/GP同步化的显着增加。氟哌啶醇或GABA（A）受体拮抗剂荷包牡丹碱的GP内离子导入诱导了短期皮层/GP同步化。引人注目的是，由局部蝇蕈醇引起的cardiac失活逆转了氟哌啶醇和TTX介导的皮质和GP之间的一致性。我们的数据表明，一个异常的皮质/BG同步，在低频率下，也可以复制没有SNc神经元的损失和纹状体细胞结构的改变。此外，我们的研究结果，这代表了一个急性和可逆的帕金森氏症的基础上受损的电缆性能，似乎与皮质和STN-GP通路之间的功能相互作用的急性变化的解释是兼容的快速深部脑刺激诱导的急性关-开转换的关键因素机制。
Pathological oscillations characterize the firing discharge of different basal ganglia (BG) stations in rat models of Parkinson's disease. Most recent literature focused on the prominence of the beta frequency band in awake rats. Yet, in 6-hydroxydopamine-lesioned animals, the firing discharge of the globus pallidus (GP) and the substantia nigra reticulata are in phase with urethane-induced slow wave cortical activity. The neuronal basis of this pathological synergy at low frequency is widely debated. In order to understand the role of substantia nigra pars compacta (SNc) signalling in the development of pathological synchronization, we performed a pharmacological inactivation of the medial forebrain bundle (MFB) through tetrodotoxin (TTX), which led to a dramatic, but reversible, reduction of the dopamine content in the striatum. This procedure caused a significant contralateral akinesia, detectable as soon as anaesthesia vanished, and lasting about 3-4 h. We sought to determine the electrophysiological counterpart of this transient Parkinsonian-like hypokinetic syndrome. Hence, we obtained the electrocorticogram (ECoG) and single unit recordings from GP and subthalamic nucleus (STN) in normal rats before and after the TTX injection in MFB. Intriguingly, the TTX-mediated inactivation of MFB induced a fast developing coherence between cortex and GP and a significant increase of the cortex/STN synchronization. The intra-GP iontophoretic delivery of haloperidol or the GABA(A) receptor antagonist bicuculline induced a short term cortex/GP synchronization. Strikingly, STN inactivation by local muscimol reversed both haloperidol- and TTX-mediated coherence between cortex and GP. Our data show that an abnormal cortical/BG synchronization, at low frequency, can be reproduced also without SNc neuronal loss and striatal cytoarchitectonic alterations. In addition, our results, which represent an acute and reversible Parkinsonism based upon impaired cable properties, seem compatible with the interpretation of acute changes of the functional interplay between cortex and the STN-GP pathway as a key factor mechanism underlying the fast deep brain stimulation-induced acute Off-On transitions.