Objective
Amyloid beta peptide (Abeta) is a normal product of the amyloid precursor protein (APP) proteolysis in the brain. While Abeta synaptotoxicity has been extensively studied as central to Alzheimer's disease (AD) pathogenesis, the mechanisms by which physiological Abeta regulates synapse function remain unknown. Utilizing two-photon excitation laser scanning microscopy combined with fluorescence lifetime imaging, FM-based imaging of synaptic vesicle recycling at the single-synapse level and electrophysiology, I aim to explore the molecular mechanisms modulating synaptic and astrocytic properties by physiological Abeta signaling and its effects on neuronal integration in acute hippocampus slice preparations.
I will investigate the potentiation of presynaptic strength by Abeta and the transducing mechanism by answering the following questions: In the hippocampus, is the Abeta-dependent potentiation of neurotransmission synapse-specific? Can APP molecules form homodimers at presynaptic and astrocytic plasma membranes? Do local changes in the conformation of APP complexes convey intracellularly the Abeta signal? I will also investigate which effectors downstream to presynaptic APP dimers are modulated to induce Abeta-dependent potentiation of neurotransmission. I will measure the distance range at which axon-released Abeta regulates presynaptic functions during neuronal activity. With electrophysiological techniques, I will characterize the effects of Abeta on the functional input-output relationship in the hippocampal network. I will finally ask whether APP molecules also exist as dimers in astrocytes and whether APP conformation is dependent on Abeta levels and on membrane specialization in the vicinity of synaptic contacts.
At the end of the project, the training in neuroimaging will offer me a great opportunity to investigate structure-functions relationship in native single synapse using cutting-edge technologies with an important impact in the field of AD.
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.
- medical and health sciences basic medicine neurology dementia alzheimer
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences optics microscopy fluorescence lifetime imaging
- natural sciences physical sciences optics laser physics
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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.
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.
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.
FP7-PEOPLE-2012-CIG
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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.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
69978 Tel Aviv
Israel
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.