Neural Mechanisms of Transcranial Current Stimulation

项目摘要 经颅电流刺激(TCS)通过放置在脑部的电极在大脑中产生小电场。 头皮。作为一种神经调节方法，TCS具有许多实际好处：它是便携的(电池- 操作)、价格低廉且易于在诊所和家中部署。由于这一简单和明显的 多功能性目前正在利用经颅电流进行的研究数量激增。 (在Clinicaltrials.gov上有500多项临床试验)。 尽管存在这种普遍性和潜在性，但即使是关于各种不同因素引起的神经变化本质的基本问题 各种形式的TCS还没有在体内得到回答。这种对潜在生物学的缺乏理解导致了 对这种方法持怀疑态度。此外，对人类使用的这项技术的改进仅限于相对 在很大程度上靠试错进行的低效过程。 该项目将在清醒的小鼠身上使用最先进的成像技术，以了解TCS如何影响变化 在神经活动方面。该项目将使用双光子成像的精致空间分辨率，以及Genetic 针对特定细胞群体的方法，揭示TCS如何影响细胞类型和层中的神经活动 具体的方式。这种高空间分辨率的技术将与高时间分辨率相辅相成 电压敏感染料成像以评估这些诱导变化的时间方面，包括 振荡的夹带作用。 这些互补的方法结合在一起，将提供TCS如何影响 前所未有的详细程度。这种洞察力--例如，理解是否所有细胞类型都受到同样的影响， 或实现有意义的神经活动夹带所需的TCS剂量-对于理性的 开发有针对性的TCS协议。

Project Summary Transcranial current stimulation (TCS) creates small electrical fields in the brain through electrodes placed on the scalp. As a method for neuromodulation, TCS carries with it many practical benefits: it is portable (battery- operated), inexpensive, and easily deployable in the clinic and at home. Due to this simplicity and apparent versatility there has been an explosion in the number of studies currently underway using transcranial currents (over 500 clinical trials on clinicaltrials.gov). Despite this ubiquity and potential, even basic questions about the nature of neural changes induced by various forms of TCS have not been answered in-vivo. This lack of understanding of the underlying biology has led to skepticism about the method. Moreover, refinement of the technique as used in humans is limited to a relatively inefficient process that proceeds largely by trial and error. This project will use state-of-the-art imaging techniques in awake mice to gain insight how TCS affect changes in neural activity. The project will use the exquisite spatial resolution of two-photon imaging, together with genetic methods to target specific cell populations, to reveal how TCS affects neural activity in a cell-type, and layer specific manner. This high-spatial resolution technique will be complemented with high temporal resolution voltage sensitive dye imaging to assess the temporal aspects of these induced changes, including the entrainment of oscillations. Together these complementary approaches will provide insight how TCS affects neural activity at an unprecedented level of detail. This insight - for instance understanding whether all cell-types are affected equally, or the TCS dose needed to achieve meaningful entrainment of neural activity - is essential for the rational development of targeted TCS protocols.