Target validation of thalamic T-type calcium channels in a mouse model of Dravet Syndrome

A common trait among genetic epilepsies is variable expressivity, or the spectrum of symptom severity in patients bearing the same genetic mutation, which suggests that clinical severity is influenced by genetic modifiers. We previously identified a modifier gene, Cacna1g, that influences seizure susceptibility in multiple mouse models of epilepsy, including a mouse model of Dravet Syndrome. One goal of this fellowship is target validation of Cacna1g and related gene Cacna1h using genetic and pharmacological tools in a mouse model of Dravet Syndrome, a critical step in determining if Cacna1g and Cacna1h may be novel targets for therapeutic intervention. The other goal of this fellowship is to use activity mapping to determine whether thalamocortical neurons are activated during seizure initiation or propagation in a mouse model of Dravet Syndrome.