The spatial and temporal regulation in the composition of the postsynaptic membrane of synapses participates to the different forms of synaptic plasticity that trigger the cellular processes of memory formation, consolidation, and retrieval. Neurotransmitter receptors move rapidly in and out of synapses by lateral diffusion. This mobility is crucial to control the number of receptors present at a given synapse. AMPA subtype glutamate receptors mediate most excitatory transmission in the brain. Thus, the equilibrium between the synaptic and extrasynaptic AMPA receptor number is crucial in controlling basal transmission and synaptic plasticity. This balance is regulated by the subunit composition of these receptors and by interacting intracellular scaffold proteins. The GluR1 subunit of AMPA receptors plays a crucial role in activity dependent synaptic plasticity. However, how trafficking of GluR1 in and out synapse is controlled remains unknown. The major aim of this project will thus be to determine the relative distribution and trafficking properties of GluR1 at unprecedented spatial and temporal resolution using a variety of ultra-high resolution fluorescence imaging approaches. Emphasis will be laid on the molecular basis for the activity dependant changes in GluR1 localization and mobility. We will study in particular the role of calcium induced phosphorylation events and GluR1-SAP97 interaction in controlling GluR1 fluxes in and out of synapses. This will provide a unique insight into the fundamental aspects of synaptic plasticity.
Call for proposal
See other projects for this call