Analysis of AMPA-Receptor Trafficking During Longterm Changes in Synaptic Plasticity

• Applicant: Professor Dr. Oliver M. Schlüter
• Subject Area: Cell Biology
• Term: from 2002 to 2006
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5386245

In recent years the cell biology of a-amino-3-hydroxy-5methyl-4-isoxazloe proprionic acid (AMPA) receptor trafficking crystallized to be an important mechanism during the expression of long-lasting changes of synaptic transmission. This was shown by the existence of silent synapses, lacking funtional AMPA receptors and the recruitment of these into the synaptic plasma membrane during long-term-potentiation (LTP) induction. Long-term-depression in contrast leads to an internalization of these receptors. The goal of this project proposal is to investigate the underlying mechanisms of AMPA receptor trafficking during the expression of LTP or LTD in more detail. It will take advantage if the already existing and partly analyzed knock out mouse lines for the AMPA receptor subunits GluR1 (also termed GluRA) and GluR2 (GluRB). I will focus on the analysis of the abnormalities in LTP and LTD expression in these mice and then attempt to rescue the phenotype using viral expression systems to express wild type and mutant proteins. The mutant versions of the receptor subunits will be particularly helpful in determining the protein-protein interactions and phosphorylation sites, which are required for the expression of LTD and LTP.

• DFG Programme: Research Fellowships
• International Connection: USA
• Cooperation Partner: Professor Dr. Robert Malenka