DYNASPINE

Nanoscale Photoactivation and Imaging of Synaptic Spine Dynamics

Coordinatore	CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE    more  Organization address address: Rue Michel -Ange 3 city: PARIS postcode: 75794 contact info Titolo: Mr. Nome: Philippe Cognome: Leconte Email: send email Telefono: +33 5 57 35 58 60 Fax: +33 5 57 35 58 01
Nazionalità Coordinatore	France [FR]
Totale costo	186˙748 €
EC contributo	186˙748 €
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-2010-IEF
Funding Scheme	MC-IEF
Anno di inizio	2012
Periodo (anno-mese-giorno)	2012-03-01   -   2014-02-28

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE  Organization address address: Rue Michel -Ange 3 city: PARIS postcode: 75794 contact info Titolo: Mr. Nome: Philippe Cognome: Leconte Email: send email Telefono: +33 5 57 35 58 60 Fax: +33 5 57 35 58 01	FR (PARIS)	coordinator	186˙748.00

Mappa

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 Obiettivo del progetto (Objective)

'Synapses are physical sites of communication that transmit and transform information between neurons in a very rapid and dynamic way. Not surprisingly, malfunctioning synapses are at the root of some of our most prevalent neurological and psychiatric disorders. As synapses are smaller than what diffraction-limited light microscopy can resolve, and densely packed in light-scattering brain tissue, it has been extremely difficult to study their physiology in mechanistic terms. As a result, we still lack an understanding of the basic dynamic organization of neurotransmitter receptors and their molecular partners at mammalian synapses. While electron microscopy provided detailed snapshots of where glutamate receptors are located inside synapses, this technique does not convey dynamic or functional information. Since existing optical approaches, such as 2-photon glutamate uncaging, do not have sufficient spatial resolution, progress in this area relies on fundamental breakthroughs in live-cell-compatible techniques relying on focused visible light. We propose to utilize novel STED superresolution microscopy to image and concurrently activate synapses in live spines by superresolution STED photo-uncaging of glutamate. STED microscopy offers optical resolution an order of magnitude higher than current 2-photon or confocal techniques, and we aim to unravel functional and structural nano-dynamics of spines and synapses during plasticity. Specifically, as part of a collaborative effort, we will (1) evaluate newly engineered photosensitive glutamate-containing compounds for superresolution STED-based photo-activation, (2) advance STED microscopy technology to concurrently activate and image synapses beyond the diffraction limit, and (3) use this new methodology to probe synaptic physiology in brain slices with unprecedented resolution. These advances will enable us to address timely questions regarding the dynamic behavior of neurotransmitter receptors in individual spines.'

Introduzione (Teaser)

Neuronal cells have strange branching extensions with little knobby bulbs on them called spines, the places where one neuron communicates with another. In pioneering work, scientists have stimulated individual synapses and imaged spine changes.