The broad goal of this project is to understand the molecular basis that underlies memory formation. Evidence suggests that the dynamic regulation of AMPA-type glutamate receptors may be a key component in mediating information storage in the brain. Glutamate released from the presynaptic nerve binds to and stimulates postsynaptic AMPA receptors (AMPARs). AMPAR expression in cerebral granule cells requires stargazin (gamma-2), a member of a closely related family of four-pass transmembrane proteins involved in synaptic AMPAR expression in distinct regions of the brain.
The aim of this project is to functionally analyze gamma-8, a stargazin homologue primarily expressed in the hippocampus, a region of the brain that mediates memory formation. Proteins that specifically interact with the unique C-terminal region of gamma-8 will be sought with the intention of understanding regulation and signaling of the AMPARs in the hippocampus. AMPAR function and trafficking in knockout mice lacking gamma-8 will be examined. These molecular and physiological studies may help to elucidate molecular mechanisms of memory formation, which could be exploited in the treatment of a wide range of neurological disorders.
