Cortical stimulation relieves parkinsonian pathological activity in vitro
Cortical stimulation relieves parkinsonian pathological activity in vitro
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DOI：
10.1111/ejn.13806
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发表时间：
2019-03-01
影响因子：
3.4
通讯作者：
Bargas, Jose
中科院分区：
文献类型：
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作者：
Aparicio-Juarez, Ariadna;Duhne, Mariana;Bargas, Jose
以前，我们已经表明，化学兴奋性驱动器，如N-甲基-D-天冬氨酸（NMDA）能够激活纹状体微电路展示神经元合奏，交替其活动产生时间序列。这项工作的目的之一是证明是否可以通过提供皮层刺激诱发类似的活动。动态钙成像使我们能够在小家鼠脑切片中以单细胞分辨率跟踪数十个神经元的活动。一系列的电刺激在皮层诱发的网络活动类似于一个由浴应用NMDA。在此之前，我们也表明，多巴胺耗尽纹状体微电路增加其自发活动产生占主导地位的经常性合奏，中断控制微电路中发现的时间序列。这种活动与帕金森病的病理活动相关。几种皮质刺激方案，如经颅磁刺激，可减少帕金森症的运动体征。在这里，我们表明，体外皮质刺激暂时消除了病理活动的多巴胺耗尽纹状体微电路关闭一些神经元，维持这种活动，并招募新的，允许网络状态之间的转换，类似于控制电路。当在L-DOPA存在的情况下给予皮层刺激时，在整个记录期间消除了帕金森病活动。目前的实验证据表明，皮质刺激，如经颅磁刺激或其他方式产生的刺激，可以允许减少左旋多巴剂量。
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.