Molecular mechanisms regulating the trafficking of calcium-permeable and -impermeable AMPA receptors in synaptic plasticity

Project Information

CP-AMPAR TRAFFICKING

Grant agreement ID: 220727

Project closed

Start date 1 July 2008

End date 30 June 2010

Funded under

• Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Total cost € 168 256,91

EU contribution € 168 256,91

Coordinated by

UNIVERSITY COLLEGE LONDON

Objective

AMPA type glutamate receptors (AMPARs) mediate fast excitatory transmission in the CNS. These receptors can be calcium-impermeable (CI AMPARs) or calcium permeable (CP AMPARs). Because insertion or removal of CI AMPARs at synapses is key to the expression of canonical forms of plasticity, such as LTP (long-term potentiation) and LTD (long-term depression), the trafficking of these receptors has been extensively studied. In various regions of the brain, CP AMPARs have been implicated in important aspects of neuronal function, including development, synaptic plasticity and cell death, yet the mechanisms regulating the synaptic expression of CP AMPARs remain unclear. This project seeks to address this issue by examining the differential trafficking of CI- and CP-AMPARs in cerebellar stellate cells (SCs), where excitatory transmission is mediated mainly by CP AMPARs. Notably, these cells exhibit a novel form of synaptic plasticity triggered by calcium entry through CP-AMPARs and expressed as a switch in synaptic receptor subtype, from CP- to CI-AMPARs. We plan to use high-resolution electrophysiology (whole-cell and outside-out patch clamp recording from SCs) combined with imaging (immunocytochemistry and single quantum dot-based tracking of AMPARs at the cell surface) to address the following questions: (1) Are transmembrane AMPAR regulatory proteins (TARPS) involved in AMPAR trafficking in SCs? These proteins underlie membrane delivery and surface trafficking of CI-AMPARs but how they regulate CP-AMPARs is unknown. (2) What cellular mechanisms underlie the activity-dependent switch in AMPAR subtype at SC synapses? Specifically, how are CI-AMPARs excluded from excitatory synapses in the basal condition and what are the regulated steps leading to their incorporation at synaptic sites – exocytosis and/or lateral diffusion? Understanding these cellular mechanisms will provide key insights into the regulation of CP-AMPARs at central synapses.

Fields of science (EuroSciVoc)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.

• natural sciences › chemical sciences › inorganic chemistry › alkaline earth metals
• natural sciences › biological sciences › biochemistry › biomolecules › proteins

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Keywords

• Calcium-permeable
• Health sciences
• Neurosciences
• cellular trafficking
• synaptic plasticity

Programme(s)

• FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Topic(s)

• PEOPLE-2007-2-1.IEF - Marie Curie Action: "Intra-European Fellowships for Career Development"

Call for proposal

FP7-PEOPLE-2007-2-1-IEF
See other projects for this call

Funding Scheme

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

UNIVERSITY COLLEGE LONDON

• EU contribution: € 168 256,91
• Address: GOWER STREET ; WC1E 6BT LONDON ;
• Activity type: Higher or Secondary Education Establishments
• Total cost: No data