Uncovering altered connectivity in epilepsy due to somatic mutations

Somatic mutations result from a new mutation that occurs later during embryonic development. Although somatic diversity is an evident feature of the brain, the extent to which somatic mutations affect the structure, function, and connectivity of neurons remains largely unexplored. In the developing brain, somatic mutations cause cortical malformations associated with pediatric intractable epilepsy. Determining the mechanisms by which somatic mutations in the brain are responsible for the altered connectivity is one of the next major challenges in the field. In this proposal, I aim to understand how somatic mutations in a contained population of neurons result in network abnormalities that lead to epilepsy. The disease mechanisms that arise from this research could lay the groundwork for new therapeutic approaches.