Cerebrocortical injuries such as stroke are a major source of disability. 
Maladaptive consequences can result from post-injury local reorganization of 
cortical circuits. For example, epilepsy is a common sequela of cortical stroke, 
but the mechanisms responsible for seizures following cortical injuries remain 
unknown. In addition to local reorganization, long-range, extra-cortical 
connections might be critical for seizure maintenance. In rats, we found that 
the thalamus, a structure that is remote from, but connected to, the injured 
cortex, was required to maintain cortical seizures. Thalamocortical neurons 
connected to the injured epileptic cortex underwent changes in HCN channel 
expression and became hyperexcitable. Targeting these neurons with a closed-loop 
optogenetic strategy revealed that reducing their activity in real-time was 
sufficient to immediately interrupt electrographic and behavioral seizures. This 
approach is of therapeutic interest for intractable epilepsy, as it spares 
cortical function between seizures, in contrast with existing treatments, such 
as surgical lesioning or drugs.