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OptoNMDA

Optical strategies to investigate NMDA receptor functional diversity and its therapeutic potential

Total Cost €

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EC-Contrib. €

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Partnership

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 Outcomes and results

 OptoNMDA project word cloud

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

light    opto    convertible    individual    neurotransmitter    polyamine    act    reversibly    optonmda    functional    dysregulation    ex    allosteric    usually    excitatory    models    glun1    pathology    critical    circuit    active    subunits    genes    innovative    stroke    retardation    vivo    preparations    optical    manipulation    deleterious    glun2    transmission    receptors    lacking    sites    pharmacological    brain    function    nmdar    class    generally    containing    tetramers    spatio    glutamate    configuration    pathologies    photo    modulating    precise    synaptic    orthosteric    consists    glun2a    proposes    compounds    neuronal    therapeutic    biophysical    anatomical    allostery    signalling    receptor    subtypes    derivatives    mental    form    tools    mammalian    ing    selectively    temporal    plasticity    inactive    strategies    fundamental    schizophrenia    genetic    subunit    nmdars    nmda    counteract    manner    physiology    hypo    encoded    physiological    synapses    population    site    play    roles    glun2b    competitive    isomerize    gated   

Project "OptoNMDA" 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 http://www.mony.fr/optoNMDA.shtml
 Total cost 185˙076 €
 EC max contribution 185˙076 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2015
 Funding Scheme MSCA-IF-EF-RI
 Starting year 2016
 Duration (year-month-day) from 2016-04-01   to  2018-07-21

 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 115˙672.00
2    ECOLE NORMALE SUPERIEURE FR (PARIS CEDEX 05) participant 69˙403.00

Map

 Project objective

NMDA receptors (NMDARs) form a class of receptors gated by glutamate, the major neurotransmitter in the mammalian brain. These receptors play fundamental roles in synaptic transmission and plasticity. They are also involved in numerous pathologies including stroke, mental retardation or schizophrenia. NMDARs are thus targets of strong therapeutic interest. NMDARs are tetramers usually composed of two GluN1 and two GluN2 subunits encoded by four different genes (GluN2A-D), resulting in a large number of receptor subtypes having distinct anatomical, biophysical, pharmacological and signalling properties. Understanding the functional role of these individual subtypes in the brain is of great importance to develop new strategies to counteract the deleterious effects of NMDAR dysregulation. However, tools allowing targeting of a specific population of NMDARs in a given neuronal circuit are currently lacking. The OptoNMDA research programme proposes the development of an innovative optical approach to selectively enhance the activity of NMDARs containing the GluN2B subunit (GluN2B-NMDARs) in ex vivo and in vivo preparations. This approach consists in developing photo-convertible polyamine derivatives that can reversibly isomerize between an inactive and active configuration with light to act on the GluN2B-NMDAR polyamine allosteric modulating site in a precise spatio-temporal manner (opto-allostery). I will study the physiological and potential therapeutic roles of these compounds by testing their effects on synaptic transmission and plasticity and on genetic models of NMDAR hypo-function. Compared to previous studies targeting orthosteric (competitive) sites, the opto-allostery approach will allow manipulation of NMDARs in a more specific and physiological manner. This project should thus provide critical novel information on NMDARs, and more generally, on the physiology and pathology of excitatory synapses.

 Publications

year authors and title journal last update
List of publications.
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 2019-07-26

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