CP-AMPAR TRAFFICKING

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

Coordinatore	UNIVERSITY COLLEGE LONDON    more  Organization address address: GOWER STREET city: LONDON postcode: WC1E 6BT contact info Titolo: Ms. Nome: Borg-Carbott Cognome: Greta Email: send email Telefono: 442077000000 Fax: 442077000000
Nazionalità Coordinatore	United Kingdom [UK]
Totale costo	168˙256 €
EC contributo	168˙256 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2007-2-1-IEF
Funding Scheme	MC-IEF
Anno di inizio	2008
Periodo (anno-mese-giorno)	2008-07-01   -   2010-06-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	UNIVERSITY COLLEGE LONDON  Organization address address: GOWER STREET city: LONDON postcode: WC1E 6BT contact info Titolo: Ms. Nome: Borg-Carbott Cognome: Greta Email: send email Telefono: 442077000000 Fax: 442077000000	UK (LONDON)	coordinator	0.00

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 Obiettivo del progetto (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.'