Abstract：
The pathophysiological progress of Parkinson\'s disease leads through degeneration of dopaminergic neurons in the substantia nigra to complete cell death and lack of dopamine in the striatum where it modulates motor functions. Transplantation of dopaminergic stem cell-derived neurons is a possible therapy to restore dopamine levels. We have previously presented multifunctional pyrolytic carbon coated leaky optoelectrical fibers (LOEFs) with laser ablated micro-optical windows (µOWs) as carriers for channelrhodopsin-2 modified optogenetically active neurons for light-induced on-demand dopamine release and amperometric real-time detection. To increase the dopamine release by stimulating a larger neuronal population with light, we present here a novel approach to generate µOWs through laser ablation around the entire circumference of optical fibers to obtain Omni-LOEFs. Cyclic voltammetric characterization of the pyrolytic carbon showed that despite the increased number of µOWs, the electrochemical properties were not deteriorated. Finally, we demonstrate that the current recorded during real-time detection of dopamine upon light-induced stimulation of neurons differentiated on Omni-LOEFs is significantly higher compared to recordings from the same number of cells seeded on LOEFs with µOWs only on one side. Moreover, by varying the cell seeding density, we show that the recorded current is proportional to the dimension of the cell population.
摘要：
帕金森病的病理生理过程通过黑质多巴胺能神经元的变性导致细胞完全死亡和纹状体中多巴胺的缺乏来调节运动功能。多巴胺能干细胞衍生的神经元的移植是恢复多巴胺水平的可能疗法。我们以前已经提出了多功能热解碳涂层泄漏光电纤维（LOEF）与激光烧蚀微光学窗口（µOWs）作为载体的通道视紫红质-2修饰的光遗传活性神经元，用于光诱导的按需多巴胺释放和安培实时检测。通过用光刺激更大的神经元群体来增加多巴胺的释放，我们在这里提出了一种新颖的方法，通过激光烧蚀在光纤的整个圆周上产生µOW，以获得Omni-LOEF。热解碳的循环伏安表征表明，尽管µOW的数量增加，电化学性能没有恶化。最后,我们证明，与仅在一侧接种有µOW的LOEF上接种的相同数量的细胞的记录相比，在光诱导刺激Omni-LOEF上分化的神经元时，实时检测多巴胺期间记录的电流显着更高。此外，通过改变细胞接种密度，我们表明，记录的电流与细胞群的大小成正比。
