Genetic And Optogenetic Dissection Of Seizures In Rett Syndrome

Rett syndrome (RTT) is a devastating neurological disorder that represents the second leading cause of intellectual disability in females. RTT patients suffer frequent and severe seizures that place a tremendous burden on patients and caregivers. Although models of RTT recapitulate many symptoms observed in patients, they exhibit few, if any, spontaneous seizures. Thus, the underlying cellular and circuit mechanisms leading to the manifestation of RTT-associated seizures remain unknown. We recently developed new models that exhibit robust RTT-associated behavioral and electrographic seizures. In this proposal, we will first dissect the specific cell types that mediate RTT-related seizures. Next, we will develop strategies to control seizure manifestation. These studies will provide new insights into the pathogenesis of seizures in RTT and may aid in the development of new strategies for their control.