Have You Tried Restarting It? Cortical Spreading Depression Shuts Down Seizures by Short-Circuiting Electrical Propagation

Spreading depression (SD) is an intense and prolonged depolarization in the central nervous systems from insect to man. It is implicated in neurological disorders such as migraine and brain injury. Here, using an in vivo mouse model of focal neocortical seizures, we show that SD may be a fundamental defense against seizures. Seizures induced by topical 4-aminopyridine, penicillin or bicuculline, or systemic kainic acid, culminated in SD at a variable rate. Greater seizure power and area of recruitment predicted SD. Once triggered, SD immediately suppressed the seizure. Optogenetic- or KCl-induced SD had a similar antiseizure effect sustained for more than 30 min. Conversely, pharmacologically inhibiting SD occurrence during a focal seizure facilitated seizure generalization. Altogether, our data indicate that seizures trigger SD, which then terminates the seizure and prevents its generalization.