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arXiv 1211.1990q-bio.NC
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帕金森病基底神经节不完全同步化的潜在机制

Potential mechanisms for imperfect synchronization in parkinsonian basal ganglia

Choongseok Park, Leonid Rubchinsky

摘要:

帕金森病患者脑内的神经活动以间歇性同步振荡动力学为特征。在β频段观察到的这种不完美的同步被认为与该疾病的运动功能减退症状有关。我们的研究探索了这种间歇性同步背后的潜在机制。本文研究了苍白球爆发神经元对丘脑底核神经元不同形式突触输入的反应。我们展示了外部苍白球(GPe)神经元如何对来自P2P细胞的输入的相位敏感,并且可以表现出与β带中的输入的间歇性锁相。这种间歇性锁相的时间特性与实验中观察到的间歇性同步具有相似之处。我们还研究了多巴胺调制参数对GPe细胞与突触输入的同步性的影响。多巴胺还影响神经元的细胞特性。我们展示了由于缺乏多巴胺引起的多巴胺神经元放电模式的变化如何导致从较低的相干状态过渡到较高的相干状态,大致匹配在正常和帕金森病状态下基底神经节中观察到的同步水平。在帕金森氏病的神经β带同步的间歇性是在模型中实现的,由于苍白球和苍白球神经元动力学的输入到苍白球的时间的相互作用,导致苍白球输出到到达的苍白球输入的相位的敏感性。因此,这里考虑的机制(通过多巴胺诱导的膜特性的变化,在发射模式的丘脑底神经元的变化)可能是一个潜在的机制,负责在帕金森氏病中观察到的间歇性同步的产生。

英文摘要:

Neural activity in the brain of parkinsonian patients is characterized by the intermittently synchronized oscillatory dynamics. This imperfect synchronization, observed in the beta frequency band, is believed to be related to the hypokinetic motor symptoms of the disorder. Our study explores potential mechanisms behind this intermittent synchrony. We study the response of a bursting pallidal neuron to different patterns of synaptic input from subthalamic nucleus (STN) neuron. We show how external globus pallidus (GPe) neuron is sensitive to the phase of the input from the STN cell and can exhibit intermittent phase-locking with the input in the beta band. The temporal properties of this intermittent phase-locking show similarities to the intermittent synchronization observed in experiments. We also study the synchronization of GPe cells to synaptic input from the STN cell with dependence on the dopamine-modulated parameters. Dopamine also affects the cellular properties of neurons. We show how the changes in firing patterns of STN neuron due to the lack of dopamine may lead to transition from a lower to a higher coherent state, roughly matching the synchrony levels observed in basal ganglia in normal and parkinsonian states. The intermittent nature of the neural beta band synchrony in Parkinson's disease is achieved in the model due to the interplay of the timing of STN input to pallidum and pallidal neuronal dynamics, resulting in sensitivity of pallidal output to the phase of the arriving STN input. Thus the mechanism considered here (the change in firing pattern of subthalamic neurons through the dopamine-induced change of membrane properties) may be one of the potential mechanisms responsible for the generation of the intermittent synchronization observed in Parkinson's disease.

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