Alzheimer s Disease, Autism Spectrum Disorders ( Asd ),...

Devyn Oliver PROJECT SUMMARY Neurological disorders such as Alzheimer’s disease, autism spectrum disorders (ASD), and schizophrenia impact behavior and cognitive processes. While the symptoms for these diseases vary, they share disruptions in synapse development and spine formation. In the mammalian nervous system, dendritic spines are small, dynamic protrusions on neurons that develop in response to increased presynaptic activity. Although spine dynamics throughout development have been well studied, very little is known about the genes involved in spine formation. A recent study in our laboratory discovered spiny projections on a group of inhibitory neurons called DD neurons in C. elegans. Using C. elegans as a model system, the goal of this project is to identify genes responsible for dendritic spine formation. Specifically, I will 1) conduct a forward genetic screen and examine candidate axon guidance molecules to identify genes involved in dendritic spine formation, and 2) examine the effect hyper- and hypo-presynaptic activity has on the development of spines using locomotory changes, such as thrashing and microfluidic assays, and cell-specific changes using channel rhodopsin and temperature sensitive alleles. Given the strong homology between C. elegans and mammalian genes, this research will help identify conserved mechanisms underlying spine formation and maintenance. Ultimately, understanding spine development will help shape the treatment and prevention of