Electroconvulsive stimulation drives cortical spreading depression dependent immediate early gene expression in mice

Electroconvulsive therapy (ECT) is a highly effective treatment for several psychiatric disorders, though its biological mechanisms remain unclear. Its therapeutic action has traditionally been attributed to the generalized seizure ECT induces. However, this view is challenged by the recent finding that electroconvulsive stimulation (ECS) can trigger a cortical spreading depression (CSD). Because CSD triggers massive intracellular molecular changes, we hypothesized that it could be a key mediator of ECTs therapeutic, plasticity-inducing effects. We observed similar neuronal oscillations following ECS in mice and patients undergoing ECT. We show that CSD drives increased expression of the imm