Project description
Elucidating the mechanisms of presynaptic refinement during postnatal development
During development, neuronal circuits are at first formed in a relatively imprecise manner. They are subsequently tightened up in a process called synaptic refinement, in which synapses and connections are added or lost. When this process goes awry, it can result in conditions such as schizophrenia and autism. N-methyl-D-aspartate (NMDA) receptors are key mediators of excitatory neurotransmission and play a pivotal role in the synaptic plasticity thought to underlie learning and memory. There are three different subunits and one is implicated in remodelling. The EU-funded DEFINE project is studying the unknown role of this subunit in presynaptic refinement during postnatal development. Insight could dramatically alter the course of often devastating diseases.
Objective
The postdoctoral project aims to investigate the mechanisms underlying sensory experience driven synaptic and circuit refinement that occurs during critical periods of brain development. Presynaptic and postsynaptic refinement involving loss and strengthening of synaptic contacts are known to occur but how these processes are coordinated and remains obscure. Failure to appropriately regulate this refinement underlies some common neurological disorders including autism and schizophrenia. The non-canonical NMDA-receptor subunit GluN3A presents a likely key factor in the timely remodelling of these circuits. This project will interrogate the completely unknown roles GluN3A plays in presynaptic postnatal refinement processes. The cellular location and trans-synaptic coordination that may define these events mediated by GluN3A will be carefully dissected through analysis of interhemispheric callosal projection axons using targeted delivery of transgenic reagents by in utero electroporation in the mouse brain. Chemogenetic and sensory deprivation approaches will provide exquisite control over activity and experience dependent roles within this refinement over critical windows of development. Revealing of cellular and molecular mechanisms that GluN3A functions through in presynaptic and axonal development will be guided by unbiased RNAseq data and explored via the latest cellular and transgenic tools. Follow up experiments assessing functional connectivity, in collaboration with colleagues at the hosting institute, will help understand the impacts on circuit function and synaptic communication arising from morphological changes of GluN3A perturbation and thus understand how healthy circuits and behaviour develop. A clearer knowledge of the molecular regulation of this synaptic restructuring from the perspective of the entire circuit and its modulation by experience during development may allow for improved therapeutic intervention in neurodevelopmental disorders.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences neurobiology
- medical and health sciences clinical medicine psychiatry schizophrenia
- medical and health sciences basic medicine neurology
- natural sciences chemical sciences electrochemistry bioelectrochemistry electroporation
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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)
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.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
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.
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.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2019
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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.
28006 Madrid
Spain
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.