Widespread activation of awake mouse cortex by electrical stimulation

Electrical stimulation is a highly-effective, temporally-precise technique to evoke neural activity in the brain, and thus is critically important for both research and clinical applications. Here, we set out to understand the time-course and spatial spread of neural activation elicited by electrical stimulation. By imaging the cortex of awake, chronically-implanted, transgenic mice during electrical stimulation, we found that a broad range of stimulation parameters led to widespread neural activation. In general, increasing current amplitude and the number of stimulation pulses progressively produced higher maximum activity and activated larger areas of cortex. However, increasing stimulation frequency above 30 Hz primarily shifted the timing, not amplitude, of peak activity. Our results demonstrate that even weak electrical stimulation widely activates neurons within awake mouse cortex.