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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.

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

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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