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.

Narrative Transcranial current stimulation is increasingly being used to alleviate the symptoms of depression, reduce epileptic seizures, and even to increase learning and cognition in healthy volunteers. However, little is known about the nature of the neural changes induced by transcranial currents. This project seeks to guide the refinement of transcranial current stimulation methods by determining how weak currents affect neural activity in mice.