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NMDADYN SIGNED

NMDA receptor diversity: from molecular dynamics to synaptic physiopathology

Total Cost €

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EC-Contrib. €

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Partnership

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 NMDADYN project word cloud

Explore the words cloud of the NMDADYN project. It provides you a very rough idea of what is the project "NMDADYN" about.

nmdar    behavioral    optochemical    raises    endogenous    thought    class    transitions    fascinated    intricate    array    mouse    subtypes    circuit    opto    initially    contains    allostery    allosteric    structural    light    neuroscientists    glutamate    insights    synaptic    vivo    chemistry    domain    roles    conformational    physiological    family    plurality    innovative    explore    subunit    neuroscience    usable    uses    levels    populations    nmdars    barriers    normal    fundamental    neuronal    ion    protein    microenvironment    engineer    questions    mechanisms    biophysical    excitatory    brain    nmda    dynamics    transmission    signaling    original    communication    comprehension    regarding    receptor    channels    strategies    functions    tight    implements    crossroads    pathology    diversity    vitro    undergoing    understand    engineering    break    revealed    plasticity    modulation    tools    lines    multiple    receptors    cellular    creates    relevance    complexity    workings    function    disease    molecular    functional    biological    regulation    temporally    undergoes    sensitive    anatomical    critical    gated    modulators    biosensors    reversible    first   

Project "NMDADYN" data sheet

The following table provides information about the project.

Coordinator
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE 

Organization address
address: RUE DE TOLBIAC 101
city: PARIS
postcode: 75654
website: www.inserm.fr

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country France [FR]
 Project website https://www.ibens.ens.fr/
 Total cost 2˙500˙000 €
 EC max contribution 2˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-AdG
 Funding Scheme ERC-ADG
 Starting year 2016
 Duration (year-month-day) from 2016-11-01   to  2021-10-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE FR (PARIS) coordinator 2˙500˙000.00

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 Project objective

NMDA receptors (NMDARs) have long fascinated neuroscientists with their distinct biophysical properties and critical roles in neuronal communication and plasticity. Recent studies have revealed that these glutamate-gated ion channels are more complex than initially thought, undergoing tight subunit-specific regulation by an array of endogenous modulators and existing as multiple subtypes, each with its own anatomical, functional and signaling properties. Such complexity raises key questions regarding the conformational changes that this multi-domain receptor undergoes, the physiological relevance of its subunit plurality and the microenvironment’s impact on receptor and circuit function. To address these challenges, this project uses innovative strategies at the crossroads of protein engineering, biological chemistry and neuroscience to achieve a molecular level control of NMDARs that is subunit-specific, reversible and usable both in vitro and in vivo. Using a bottom-up approach, it contains four aims covering molecular, cellular and behavioral levels. The first two investigate NMDAR structural mechanisms and exploit this knowledge to develop new optochemical receptor tools. The next two address physiological questions using these tools as well as original biosensors and novel mouse lines. Aim 1: Characterize NMDAR conformational dynamics and allosteric transitions Aim 2: Engineer a family of light-controlled NMDARs (‘Opto-allostery’) Aim 3: Understand the role of specific NMDAR populations in neuronal functions Aim 4: Explore the receptor’s synaptic microenvironment in normal and disease states This multi-scale project creates and implements the spatially and temporally sensitive tools required to break the barriers to our understanding of NMDAR diversity and modulation. The results will provide fundamental insights into the intricate workings of an essential class of brain receptors and further our comprehension of neuronal excitatory transmission and pathology.

 Publications

year authors and title journal last update
List of publications.
2019 Y. Otsu, E. Darcq, K. Pietrajtis, F. Mátyás, E. Schwartz, T. Bessaih, S. Abi Gerges, C. V. Rousseau, T. Grand, S. Dieudonné, P. Paoletti, L. Acsády, C. Agulhon, B. L. Kieffer, M. A. Diana
Control of aversion by glycine-gated GluN1/GluN3A NMDA receptors in the adult medial habenula
published pages: 250-254, ISSN: 0036-8075, DOI: 10.1126/science.aax1522
Science 366/6462 2019-12-17
2020 Joanna Sikora, Brigitte L. Kieffer, Pierre Paoletti, Abdel-Mouttalib Ouagazzal
Synaptic zinc contributes to motor and cognitive deficits in 6-hydroxydopamine mouse models of Parkinson\'s disease
published pages: 104681, ISSN: 0969-9961, DOI: 10.1016/j.nbd.2019.104681
Neurobiology of Disease 134 2019-12-17
2019 Pierre Paoletti, Graham C. R. Ellis-Davies, Alexandre Mourot
Optical control of neuronal ion channels and receptors
published pages: 514-532, ISSN: 1471-003X, DOI: 10.1038/s41583-019-0197-2
Nature Reviews Neuroscience 20/9 2019-12-17
2017 Joana S Ferreira, Thomas Papouin, Laurent Ladépêche, Andrea Yao, Valentin C Langlais, Delphine Bouchet, Jérôme Dulong, Jean-Pierre Mothet, Silvia Sacchi, Loredano Pollegioni, Pierre Paoletti, Stéphane Henri Richard Oliet, Laurent Groc
Co-agonists differentially tune GluN2B-NMDA receptor trafficking at hippocampal synapses
published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.25492
eLife 6 2019-06-13
2018 Viktoria Klippenstein, Laetitia Mony, Pierre Paoletti
Probing Ion Channel Structure and Function Using Light-Sensitive Amino Acids
published pages: 436-451, ISSN: 0968-0004, DOI: 10.1016/j.tibs.2018.02.012
Trends in Biochemical Sciences 43/6 2019-06-13
2018 David Stroebel, Mariano Casado, Pierre Paoletti
Triheteromeric NMDA receptors: from structure to synaptic physiology
published pages: 1-12, ISSN: 2468-8673, DOI: 10.1016/j.cophys.2017.12.004
Current Opinion in Physiology 2 2019-06-13
2017 Viktoria Klippenstein, Christian Hoppmann, Shixin Ye, Lei Wang, Pierre Paoletti
Optocontrol of glutamate receptor activity by single side-chain photoisomerization
published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.25808
eLife 6 2019-06-13
2018 Teddy Grand, Sarah Abi Gerges, Mélissa David, Marco A. Diana, Pierre Paoletti
Unmasking GluN1/GluN3A excitatory glycine NMDA receptors
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-07236-4
Nature Communications 9/1 2019-06-06
2019 Jean‐Baptiste Esmenjaud, David Stroebel, Kelvin Chan, Teddy Grand, Mélissa David, Lonnie P Wollmuth, Antoine Taly, Pierre Paoletti
An inter‐dimer allosteric switch controls NMDA receptor activity
published pages: e99894, ISSN: 0261-4189, DOI: 10.15252/embj.201899894
The EMBO Journal 38/2 2019-06-06
2018 Lulu Yao, Teddy Grand, Jesse E. Hanson, Pierre Paoletti, Qiang Zhou
Higher ambient synaptic glutamate at inhibitory versus excitatory neurons differentially impacts NMDA receptor activity
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-06512-7
Nature Communications 9/1 2019-06-06

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