The roles of juvenile NMDA receptors in synapse maturation and elimination and their association with cognition

Projektinformationen

NMDAR-synprun

ID Finanzhilfevereinbarung: 330284

Abgeschlossenes Projekt

Startdatum 1 März 2013

Enddatum 28 Februar 2015

Finanziert unter

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

Gesamtkosten € 166 336,20

EU-Beitrag € 166 336,20

Koordiniert durch

FUNDACION PARA LA INVESTIGACION MEDICA APLICADA FIMA
Spain

Ziel

The aim of the project is to understand how the NMDA receptor subunit NR3A is involved in selective synapse elimination (“pruning”) during development and how the abnormal expression of NR3A found in mental disorders such as Schizophrenia, Alzheimer´s disease and Huntington correlates with the reduction of functional synapses and deficits in the cognitive function. Importantly, the Host lab has already proved that restoring the normal NR3A expression levels reverses both, the spine lost and the cognitive impairment in mouse models. My working hypothesis is that NR3A and its associated signalling complexes act locally as a brake on the maturation of specific synapses to direct targeted, activity-dependent destabilisation and pruning. I will test this hypothesis by: 1) studying mechanisms that underlie the inhibitory effects of NR3A on synapse stabilization or its facilitation of pruning, 2) evaluating how genetic manipulation of NR3A signalling pathways affects cognition. Candidate inhibition/pruning mechanisms that will be tested here include destabilizing effects of NR3A in NMDA receptor mobility within the plasma membrane, altered NMDAR synaptic localization, and recruitment via intracellular domains of NR3A of signalling complexes driving synapse destabilization and disassembly. Specifically, I will use a combination of established and recently developed imaging, molecular biology, electrophysiology and behavioural techniques in primary neuronal cultures, brain slices and the whole animal. The proposed work not only will reveal the molecular links between NR3A expressions, neuronal connectivity and cognitive function in the normal brain, but also will provide and validate suitable targets for the therapeutic intervention in mental disorders where synaptic lost underlies deficits in cognition.

Wissenschaftliches Gebiet

• natural sciences › biological sciences › neurobiology › cognitive neuroscience
• medical and health sciences › basic medicine › neurology › dementia › alzheimer
• medical and health sciences › medical biotechnology › genetic engineering
• medical and health sciences › clinical medicine › psychiatry › schizophrenia
• natural sciences › biological sciences › molecular biology

Programm/Programme

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

Thema/Themen

• FP7-PEOPLE-2012-IEF - Marie-Curie Action: "Intra-European fellowships for career development"

Aufforderung zur Vorschlagseinreichung

FP7-PEOPLE-2012-IEF
Andere Projekte für diesen Aufruf anzeigen

Finanzierungsplan

MC-IEF - Intra-European Fellowships (IEF)

Koordinator

FUNDACION PARA LA INVESTIGACION MEDICA APLICADA FIMA

Kontakt Verwaltung

Ana Iglesias Garcia (Ms.)

• EU-Beitrag: € 166 336,20
• Adresse: AVENIDA DE PIO XII 55 ; 31008 Pamplona ; Spanien
• Region: Noreste › Comunidad Foral de Navarra › Navarra
• Aktivitätstyp: Research Organisations
• Gesamtkosten: Keine Daten