A basis for the pathological oscillations in basal ganglia: the crucial role of dopamine.
A basis for the pathological oscillations in basal ganglia: the crucial role of dopamine.
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DOI：
10.1097/wnr.0b013e328342ba50
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发表时间：
2011-03-09
期刊：
影响因子：
1.7
通讯作者：
Dostrovsky JO
中科院分区：
文献类型：
--
作者：
Weinberger M;Dostrovsky JO
帕金森病是一种进行性神经退行性运动障碍，其特征在于运动减少和缓慢（运动不能和运动迟缓）、肌肉僵硬和震颤。该疾病的核心病理是投射到纹状体和其他基底神经节核的黑质部中脑多巴胺能神经元的变性。纹状体是基底神经节的主要输入结构，接受来自许多皮质区和丘脑核团的兴奋性投射。纹状体的输出神经元，称为中型棘神经元，是γ-氨基丁酸能（GABA能）的，并且投射到苍白球内部和外部以及黑质网状部，其也是GABA能的。基底神经节内的另一个核团是丘脑底核，它接受直接的皮质输入和来自苍白球外部的输入，其丘脑能神经元投射到苍白球内部和黑质网状部（见图1）。直到最近，人们还认为纹状体多巴胺能输入的丧失导致苍白球内部和黑质网状部的过度活跃，这导致了运动功能减退的症状该模型通常被称为“速率”模型，为帕金森病中出现的运动迟缓和运动不能提供了非常合理的解释，因为提出的GABA能输出核、苍白球内侧和黑质网状部的过度活跃将导致丘脑中继到运动皮质的活动减退，从而导致皮质兴奋性降低以及运动缓慢和减少。最初的实验证据为该模型提供了支持，并且是在丘脑底核和苍白球内核中引入苍白球切开术和深部脑刺激以治疗帕金森病的基础。然而，最近的研究结果对该模型的有效性产生了怀疑，并促使重新检查帕金森病症状的潜在机制[1]。特别是，在动物模型和帕金森病患者的皮质基底神经节回路中的电生理记录表明，慢性多巴胺耗竭与放电的改变有关。
Parkinson’s disease is a progressive neurodegenerative movement disorder characterized by reduction and slowness of movement (akinesia and bradykinesia), muscle rigidity, and tremor. The core pathology of the disease is the degeneration of midbrain dopaminergic neurons in the substantia nigra pars compacta that project to the striatum and other basal ganglia nuclei. The striatum is the main input structure of the basal ganglia and receives excitatory projections from many cortical areas and thalamic nuclei. The output neurons of the striatum, named as medium spiny neurons, are γ-aminobutyric acidergic (GABAergic) and project to both the globus pallidus internus and externus, and to substantia nigra pars reticulata, which are also GABAergic. The other nucleus within the basal ganglia is the subthalamic nucleus that receives direct cortical inputs and an input from the globus pallidus externus and its glutamatergic neurons project to the globus pallidus internus and substantia nigra pars reticulata (see Fig. 1).Until recently it was thought that the loss of dopaminergic inputs to the striatum led to hyperactivity of the globus pallidus internus and substantia nigra pars reticulata, and this caused hypokinetic motor symptoms. This model, frequently termed as the ‘rate’model, provided a very plausible explanation for the bradykinesia and akinesia that develops in Parkinson’s disease, as the proposed hyperactivity of the GABAergic output nuclei, globus pallidus internus, and substantia nigra pars reticulata would lead to hypoactivity in the thalamic relay to motor cortex, thus, leading to a decreased cortical excitability and slowness and reduction of movements. Initial experimental evidence provided support for this model and was the basis for introduction of pallidotomies and deep brain stimulation in the subthalamic nucleus and globus pallidus internus for treating Parkinson’s disease. However, recent findings have cast doubt on the validity of this model and prompted a reexamination of the mechanisms underlying the symptoms of Parkinson’s disease [1]. In particular, electrophysiological recordings in corticobasal ganglia circuits in animal models and patients with Parkinson’s disease showed that chronic dopamine depletion is associated with alterations in firing