Molecular mechanisms of AMPA receptor phosphorylation underlying synaptic plasticity

Synaptic plasticity, the neural substrate of learning and memory, is essential throughout life and its decline impedes healthy aging. Phosphorylation-dependent changes in the function and trafficking of AMPA-type glutamate receptors drive synaptic plasticity, but the molecular mechanisms are poorly understood. To determine how phosphorylation of the intracellular Ctails of AMPA receptors and their auxiliary proteins modulates their structure and function we will combine quantitative cross-linking coupled to mass spectrometry and patch-clamp electrophysiology. This novel combination of interdisciplinary approaches will provide insight into the key protein-protein interactions that underlie a fundamental process responsible for synaptic plasticity.