Tremendous advancement in genetic studies helped to identify the involvement of many genes in the etiology of epilepsy and autism. However, our understanding of the pathways leading from a genetic mutation to abnormal brain function is still in its infancy.
Ion channels mediate neuronal communication and firing. One of the pivotal families of ion channels are the voltage-gated sodium channels (Nav). Mutations in Nav were identified in epilepsy and autism patients, however, connecting the dots between Nav dysfunction and the resulting diseases have proven to be a formidable task. In order to bridge this gap we use mouse models mimicking the human genetic mutation and unveil perturbations of neuronal function on cellular, network and behaving animal levels.
Dravet syndrome is an intractable childhood-onset epilepsy caused by loss of function mutations in Nav1.1. Dravet syndrome symptoms begin during the first year of life, with seizures often associated with fever, and progress to refractory and frequent seizures. Additionally Dravet patients develop cognitive deficit, autistic-like behaviours, hyperactivity and premature death.
Using Dravet syndrome mouse model we:
Understand the relationship between seizures and cognitive impairment in Dravet Syndrome.
Explore functional interactions between different voltage gated sodium channels and compensatory mechanisms in Dravet Syndrome.