Cerebrocortical injuries after stroke are a major source of disability. Epilepsy is a common sequela of cortical stroke, but the mechanisms responsible for seizures following cortical injuries remain unknown. In addition to local neuronal reorganization, long-range connections outside the cortex have been hypothesized to be critical for seizure maintenance.
In this study, researchers found that the thalamus, a structure that is remote from, but connected to, the injured cortex, was required to maintain cortical seizures in rats. Thalamocortical neurons became hyperexcitable and underwent changes in HCN channel expression. 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. The authors suggest that this approach may be useful for intractable epilepsy, as it spares cortical function between seizures, in contrast with existing treatments, such as surgical lesioning or drugs.
Paz JT, Davidson TJ, Frechette ES, Delord B, Parada I, Peng K, Deisseroth K, Huguenard JR: Closed-loop optogenetic control of thalamus as a tool for interrupting seizures after cortical injury. Nature Neuroscience [Epub ahead of print, November 7, 2012: doi:10.1038/nn.3269].
