Striatal origin of the pathologic beta oscillations in Parkinson's disease
Striatal origin of the pathologic beta oscillations in Parkinson's disease
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DOI：
10.1073/pnas.1107748108
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发表时间：
2011-07-12
影响因子：
11.1
通讯作者：
Kopell, N.
中科院分区：
文献类型：
--
作者：
McCarthy, M. M.;Moore-Kochlacs, C.;Kopell, N.
β 频率（8-30 Hz）的增强振荡是帕金森病患者基底神经节和皮质的标志性神经动态病理学。这些病理性β振荡背后的机制仍然难以捉摸。在这里，我们使用数学模型发现，纹状体中型多棘神经元之间的抑制性相互作用可以产生强大的β振荡。突触 GABAa 电流和内在膜 M 电流的相互作用促进了 beta 频率范围内的群体振荡。胆碱能驱动水平的增加（一种与帕金森病纹状体相关的疾病）会导致纹状体模型中的β振荡增强。我们通过实验证明，将胆碱能激动剂卡巴胆碱直接输注到清醒的正常啮齿动物的纹状体中，而不是输注到邻近的皮层中，会在局部场电位中引起显着的β频率振荡。这些结果为正常纹状体网络动力学的放大作为帕金森病中β频率振荡增强的机制提供了证据。
Enhanced oscillations at beta frequencies (8-30 Hz) are a signature neural dynamic pathology in the basal ganglia and cortex of Parkinson's disease patients. The mechanisms underlying these pathological beta oscillations remain elusive. Here, using mathematical models, we find that robust beta oscillations can emerge from inhibitory interactions between striatal medium spiny neurons. The interaction of the synaptic GABAa currents and the intrinsic membrane M-current promotes population oscillations in the beta frequency range. Increased levels of cholinergic drive, a condition relevant to the parkinsonian striatum, lead to enhanced beta oscillations in the striatal model. We show experimentally that direct infusion of the cholinergic agonist carbachol into the striatum, but not into the neighboring cortex, of the awake, normal rodent induces prominent beta frequency oscillations in the local field potential. These results provide evidence for amplification of normal striatal network dynamics as a mechanism responsible for the enhanced beta frequency oscillations in Parkinson's disease.