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Cortical stimulation relieves parkinsonian pathological activity in?vitro in?vitro

机译:皮质刺激在体外缓解了帕金森病病理活性

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Abstract Previously, we have shown that chemical excitatory drives such as N ‐methyl‐ d ‐aspartate ( NMDA ) are capable of activating the striatal microcircuit exhibiting neuronal ensembles that alternate their activity producing temporal sequences. One aim of this work was to demonstrate whether similar activity could be evoked by delivering cortical stimulation. Dynamic calcium imaging allowed us to follow the activity of dozens of neurons with single‐cell resolution in mus musculus brain slices. A train of electrical stimuli in the cortex evoked network activity similar to the one induced by bath application of NMDA . Previously, we have also shown that the dopamine‐depleted striatal microcircuit increases its spontaneous activity generating dominant recurrent ensembles that interrupt the temporal sequences found in control microcircuits. This activity correlates with parkinsonian pathological activity. Several cortical stimulation protocols such as transcranial magnetic stimulation reduce motor signs of Parkinsonism. Here, we show that cortical stimulation in?vitro temporarily eliminates the pathological activity from the dopamine‐depleted striatal microcircuit by turning off some neurons that sustain this activity and recruiting new ones that allow transitions between network states, similar to the control circuit. When cortical stimulation is given in the presence of L‐ DOPA , parkinsonian activity is eliminated during the whole recording period. The present experimental evidence suggests that cortical stimulation such as that generated by transcranial magnetic stimulation, or otherwise, may allow reduce L‐ DOPA dosage.
机译:摘要以前,我们已经表明,诸如N-甲基-D-海地(NMDA)之类的化学兴奋驱动器能够激活表现出替代其活性产生时间序列的神经元合奏的纹状体微电路。这项工作的一个目的是通过提供皮质刺激来证明是否可以诱发类似的活动。动态钙成像使我们遵循数十个神经元的活性,用单细胞分辨率在Mus Musculus脑切片中。皮质诱发网络活动中的电气刺激火车类似于由NMDA的浴应用诱导的网络活动。以前,我们还表明,多巴胺耗尽的纹状体微电路增加了其自发性活性,产生显性复发集合,其中断控制微电路中发现的时间序列。该活动与Parkinsonian病理活动相关联。几种皮质刺激方案,如经颅磁刺激减少了帕金森主义的电机迹象。在这里,我们表明:体外皮质刺激暂时消除了通过关闭维持这项活动的一些神经元的多巴胺耗尽的纹状体微电路的病理活性,并招募允许网络状态之间的过渡,类似于控制电路。当在L- DOPA存在下给出皮质刺激时,在整个记录期间消除了PARKINSONIAN活动。本实验证据表明皮质刺激,例如经颅磁刺激产生的,或者以其他方式产生的刺激,可以允许减少L- DOPA剂量。

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