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

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.

Fields of science (EuroSciVoc)

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Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2015

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Coordinator

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 115 672,50
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 115 672,50

Participants (1)

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