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Molecular Mechanisms of GABAergic synapse formation: spatial segregation in cortical inhibitory inputs

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Neuronal circuitries underlying the function of the mammalian cerebral cortex collectively constitute one of the most complex biological systems. As such, unraveling the mechanisms that control their development represents one of the most challenging questions in Science. Understanding this process is also an imperative need in biomedicine, because abnormal wiring is thought to cause severe neuropsychiatric disorders.

During development, the astonishing specificity of neuronal wiring is achieved by the coordination of multiple cues, which first guide axons to the right target area, then to the proper cellular partner and, finally, to the precise subcellular compartment onto which synapses will be formed. Subcellular segregation of synapses occurs for all types of inputs, but it reaches its highest diversity for inhibitory GABAergic terminals. Much is known about the general machinery controlling axon guidance in the developing brain; in contrast, the mechanisms of synapse segregation remain largely unknown.

The goal of this proposal is to identify molecules involved in subcellular domain-restricted GABAergic synapse targeting. To this aim, we will carry out a candidate approach strategy and an unbiased genomic screening comparing neurons obtained from specific populations of interneurons that make synapses into different subcellular compartments. Promising candidates will then be tested by gain and loss of function experiments using confocal and two-photon microscopy in vivo and cell biology analyses in vitro. To confirm the functional relevance of candidate molecules, we will combine optogenetics tools with gain and loss of function approaches in slices cultures. Unraveling the mechanisms that control the precise spatial organization of synapse formation during development may have a major impact in our knowledge, from understanding plasticity in the healthy brain to identifying wiring abnormalities in disease.

Wissenschaftliches Gebiet

Programm/Programme

Thema/Themen

Aufforderung zur Vorschlagseinreichung

ERC-2012-StG_20111109
Andere Projekte für diesen Aufruf anzeigen

Finanzierungsplan

ERC-SG - ERC Starting Grant

Gastgebende Einrichtung

KING'S COLLEGE LONDON
EU-Beitrag
€ 1 133 038,53
Adresse
STRAND
WC2R 2LS London
Vereinigtes Königreich

Auf der Karte ansehen
Region
London Inner London — West Westminster
Aktivitätstyp
Higher or Secondary Education Establishments
Kontakt Verwaltung
Paul Labbett (Mr.)
Hauptforscher
Beatriz Rico Gozalo (Dr.)
Links
Gesamtkosten
Keine Daten

Begünstigte (2)

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Letzte Aktualisierung: 24 September 2017

Mein Booklet

Permalink: https://cordis.europa.eu/project/id/310021/de

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