Investigating the synaptic trafficking of endogenous AMPARs

Project Summary Changes to synaptic architecture underlie the cellular basis for learning and memory and impaired synaptic function and plasticity are observed in numerous brain diseases and disorders including epilepsy, autism, and schizophrenia. The synthesis and precise delivery of AMPA-type glutamate receptors (AMPARs) to the postsynaptic membrane is a critical mechanism for proper basal synaptic function and plasticity. How new receptors are delivered to specific synapses and how receptor trafficking is influenced by neural activity remain important questions. A major limitation for addressing these questions is the current reliance on non- physiological, overexpressed receptors to study neuronal synaptic protein trafficking pathways. To overcome this hurdle, I have developed and validated a new toolkit that allows me to label endogenous AMPARs and control their trafficking. I propose to leverage these new tools to investigate where, when, and how new AMPARs are delivered to specific synapses under basal conditions and following diverse forms of synaptic plasticity.