This is an individual National Research Service Award for pre-doctoral research training, which provides support for promising doctoral candidates who will be performing dissertation research and training in a scientific health-related field. Mutations in L-type voltage gated calcium channels (LTCs) are associated with autism and other neurodevelopmental disorders. The goal of this project is to investigate how LTCs regulate neural progenitor cell (NPC) proliferation and differentiation. Neural development involves a series of coordinated events that balance maintenance and proliferation of NPCs with the differentiation of daughter cells to generate the neuronal populations that comprise the mature cerebral cortex. LTCs such as CaV1.2 convert electrical signals into calcium signals that control biochemical pathways and activate programs of gene expression in the developing nervous system. A gain of function mutation in CaV1.2 leads to Timothy Syndrome (TS), a multi-systemic disorder characterized by autism and mental retardation. This project will use a transgenic mouse model for TS to investigate both the regulation of CaV1.2 during development and the mechanisms by which these channels control NPC differentiation in vitro and in vivo. These studies will expand understanding of how activity regulates brain development and will provide new insights into the underlying pathophysiology of autism and mental retardation.