Grant: Project Grant

Memory formation requires the production of new proteins that modify connections (synapses) between neurons in the brain. These proteins support long-lasting changes in the strength and size of synapses within neural circuits. Improper control over protein synthesis results in memory impairments and is implicated in synaptic dysfunction/loss in brain diseases including Alzheimer's disease (AD). The overall goal of this project is to define specific protein synthesis mechanisms that determine where, when, and how specific mRNAs are translated into protein at synapses to support their plasticity and utilize these mechanisms to alleviate cognitive deficits in diseases such as AD. To achieve this goal, we will study a pathway we uncovered involving the molecule Fragile X Related Protein 1 (FXR1P). The FXR1P pathway is unique in its ability to selectively restrain the synthesis and activity-dependent delivery of the glutamate receptor subunit GluA2 to synapses in order to control synaptic plasticity and memory formation. Our Objectives are to: 1) Demonstrate how FXR1P regulates structural/functional plasticity of individual synapses, and 2) Determine how regulation of FXR1P and GluA2 can be used to mitigate synaptic deficits and memory impairments in AD models. This research will reveal new concepts regarding the healthy and diseased brain, and potentially identify a strategy for improving memory loss and rescuing the lost potential of individuals with cognitive impairments.