Closed-loop optogenetic control of thalamus as a tool for interrupting seizures after cortical injury.
Jeanne T. Paz,Thomas J. Davidson,Eric S. Frechette,Bruno Delord,Isabel Parada,Kathy Peng,Karl Deisseroth,John R. Huguenard +7 more
TLDR
In rats, it was found that the thalamus, a structure that is remote from, but connected to, the injured cortex, was required to maintain cortical seizures, and a closed-loop optogenetic strategy revealed that reducing their activity in real-time was sufficient to immediately interrupt electrographic and behavioral seizures.Abstract:
In this study, the authors report that a focal cortical injury can induce changes in the excitability of thalamocortical neurons that contributes to the maintenance of cortical seizures. In addition, silencing these neurons via a closed-loop optogenetic approach is sufficient to interrupt these seizures. 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.read more
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Multimodal fast optical interrogation of neural circuitry
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