Project description
At the site of information transmission, the transmitter finally gets the attention it deserves
Donald Hebb first postulated the presence of activity-dependent changes in neurons in his seminal book published in 1949. Since then, scientists have advanced our understanding of neuronal interactions tremendously, evaluating synaptic plasticity with ever-increasing temporal and spatial resolution and, in some cases, even correlating electrophysiological and molecular changes with organism behaviour. However, despite the intense interest in and significance of what happens at the synapse relative to cognition and behaviour, the presynaptic changes have largely taken a backseat to the postsynaptic changes. The EU-funded project PreSynPlast is using a variety of in vitro preparations and electrophysiological and molecular studies to provide an unprecedented window onto presynaptic plasticity. Outcomes will have implications for our understanding of the brain, for computational models and computing, and for novel angles on common diseases.
Objective
                                The ambitious goal of this project is to reveal the molecular mechanisms of presynaptic plasticity in the vertebrate brain. Synaptic plasticity occurs in the form of alterations in both presynaptic neurotransmitter release and postsynaptic receptor function. However, due to technical reasons and in contrast to intensely studied postsynaptic plasticity, the presynaptic half of the brains synaptic plasticity remains enigmatic. This is a crucial knowledge gap for our understanding of learning and memory.
	My ambitious aim is therefore to uncover the molecular and biophysical mechanisms of presynaptic plasticity. Building on my strong track record in presynaptic research, my group made a technical breakthrough by establishing patch-clamp recordings from small nerve terminals of cultured neocortical neurons with unprecedented high resolution. In addition, we use an innovative super-resolution-microscopy approach resolving the rearrangement of proteins within the presynaptic neurotransmitter release site, which allows high-throughput screening of all major classes of synaptic genes for their involvement in presynaptic plasticity. To reveal the neuron- and plasticity-type specificity, the identified molecular pathways will be analysed in different types of neurons in culture and acute brain slices. Building on these unique abilities, I will also investigate physiological and pathophysiological modulations of presynaptic plasticity. Specifically, I will test the hypothesis that metabolic constraints regulate presynaptic plasticity and that the amyloid pathology of Alzheimers disease impacts presynaptic plasticity.
	Thus, for the first time in the history of neuroscience, neocortical nerve terminals can be investigated with direct electrophysiological recordings and super-resolution microscopy providing unprecedented spatial and temporal resolution for the analysis of presynaptic plasticity. The results could pave the way for new approaches treating neurological diseases.
                            
                                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 basic medicine neurology dementia alzheimer
- natural sciences physical sciences optics microscopy super resolution microscopy
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine pathology
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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.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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            Topic(s)
            
              
              
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                  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.
ERC-COG - Consolidator Grant
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              Call for proposal
                
                  
                  
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(opens in new window) ERC-2019-COG
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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.
04109 Leipzig
Germany
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