New waves: Rhythmic electrical field stimulation systematically alters spontaneous slow dynamics across mouse neocortex

The signature rhythm of slow-wave forebrain activity is the large amplitude, slow oscillation (SO: ~1 Hz) made up of alternating synchronous periods of depolarizing and hyperpolarizing states at the single cell and network levels. On each wave, the SO originates at a unique location and propagates across the neocortex. Attempts to manipulate SO activity using electrical fields have been shown to entrain cortical networks and enhance memory performance. However, neural activity during this manipulation has remained elusive due to methodological issues in typical electrical recordings. Here we use voltage-sensitive dye (VSD) imaging in a bilateral cortical preparation of urethane-anesthetized mice to track SO cortical activity and its modulation by sinusoidal electrical field stimulation applied to frontal regions. We show that under spontaneous conditions, the SO propagates in two main opposing directional patterns along an anterior lateral – posterior medial axis. Rhythmic field stimulation alters spontaneous propagation to reflect activity that repeats cycle after cycle with distributed and varied anterior initiation zones and a consistent termination zone in the posterior somatosensory cortex. Our results show that slow electrical field stimulation stereotypes ongoing slow cortical dynamics during sleep-like states. Author Contributions A.G., J.K.A., M.H.M. and C.T.D. designed the study. A.G. and J.K.A. performed the experiments. A.G. analyzed the data. A.G. wrote the manuscript, which all authors commented on and edited. C.T.D. and M.H.M. supervised the study.