ESR1
    ESR2
    ESR3
    ESR4
    ESR5
    ESR6
    ESR7
    ESR8
    ESR9
    ESR10
    ESR11
    ER1
    ER2
    ER3


Project Co-ordinator:

Prof. Leszek Kaczmarek
http://neurogene.nencki.gov.pl
l.kaczmarek@nencki.gov.pl
Nencki Institute
Warsaw, POLAND

 

Project Manager:

Ms. Marta Rucinska
m.rucinska@nencki.gov.pl
Nencki Institute
Warsaw, POLAND

 

Recruitment Co-ordinator

Prof. Alexander Dityatev
alexander.dityatev@dzne.de
Deutsches Zentrum fur
Neurodegenerative Erkrankungen
Magdeburg, GERMANY

 

Training Co-ordinator

Prof. Robert Pawlak
R.Pawlak@exeter.ac.uk
University of Exeter Medical School
Exeter, UK

ESR10: ECM and synapse dynamics (lead: ENS, partners: DZNE-2a, UCL, SVIDA)

Alexandra Nothnagel

nothnage@biologie.ens.fr

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This PhD project is located at the Ecole Normale Superieure (ENS), Paris, and is supervised by Antoine Triller at the Institute of Biology (IBENS). The project aims at understanding how the extracellular matrix (ECM) regulates receptor trafficking in basal conditions and during synaptic plasticity.

Chemical transmission through synapses is a key factor in neuronal communication. Efficient and precise communication requires synapses to be stable and adaptable. Although the organization and function of the synapse is extremely stable, at least one of its elements, the neurotransmitter receptors, happen to move. They diffuse along the cell membrane to get in and out of the synapse at a highly dynamic rate. Among the structural elements that can regulate this diffusion,  a candidate of choice is the gelatinous mesh of proteins and sugars that surrounds all cells, and termed the extracellular matrix (ECM).

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Fluorescence image of mouse neocortical neurons (30 days in vitro) showing three neurons positive for parvalbumin (red). One of them is ensheathed in a perineuronal net of extracellular matrix (green). Neurons are identified by the blue staining of the cell’s nucleus.

Our team hypothesizes that changes in structure and composition of the ECM affect the movement of neuronal receptors in and out of synapses, subsequently affecting the strength of transmission across the synapse. In particular, we study parvalbumin interneurons, a type of neuron of the cortex specialized in the control and coordination of information flow, that is covered in a peculiar ECM forming a dense perineuronal net. To test this hypothesis, we will modify the composition of the ECM and use super-resolution PALM-STORM light microscopy (see Specht et al., Neuron, 2013), tracking of single molecule diffusion in “real” time with quantum dots (QD) or SPT-PALM technologies to study the subsequent changes in synaptic innervation and receptor dynamics of this neuronal population.

For more information about research in our group, please see our website (http://www.ibens.ens.fr/spip.php?rubrique22) and articles related to the project, below:

Quantitative nanoscopy of inhibitory synapses: counting gephyrin molecules and receptor binding sites. Specht CG, Izeddin I, Rodriguez PC, El Beheiry M, Rostaing P, Darzacq X, Dahan M, Triller A. Neuron. 2013 Jul 24;79(2):308-21.

Synaptic structure and function. Triller A, Sheng M. Curr Opin Neurobiol. 2012 Jun;22(3):3635.

A crosstalk between β1 and β3 integrins controls glycine receptor and gephyrin trafficking at synapses. Charrier C, Machado P, Tweedie-Cullen RY, Rutishauser D, Mansuy IM, Triller A. Nat Neurosci. 2010 Nov;13(11):1388-95.

 

The "Institut de Biologie de l’ENS" (IBENS) is part of the ENS. ENS is a higher education institution for advanced studies, and a prestigious French research center (http://www.ens.fr). IBENS represents a unique environment fostering excellence in research. Multidisciplinary research is a strong point and is reinforced by collaborations with the outstanding ENS departments of physics, chemistry, mathematics, cognitive studies and computing science. Recent development at IBENS has focused on innovative, emerging optical techniques such as single-particle tracking to study receptor dynamics, high-speed two-photon imaging, PALM/STORM, and optical and electrical recordings in vivo. Other technological platforms at IBENS include electron microscopy, genomics, and protein production.