Objective
This proposal describes experiments aimed at defining the multiple roles of vesicular glutamate transporters (VGLUTs) in central synapses. Classically, VGLUTs transport glutamate from the cytoplasm into synaptic vesicles. Deletion of these genes disrupts synaptic glutamate release and their expression suffices to determine neurons as glutamatergic. We recently discovered that VGLUTs control additional key parameters such as quantal size and vesicular release probability, suggesting that they are fundamental regulators of synaptic strength and synaptic plasticity. To study these novel functions, we will first address whether the number of VGLUTs per vesicle (VGLUT content) can affect the amount of stored glutamate and in addition, the probability of vesicle release. We will subsequently explore the underlying mechanisms. Second, we will test the hypothesis that different VGLUT paralogs contribute to functional differences in discrete synapse populations, as implied by our preliminary data and the distribution pattern of the two main paralogs VGLUT1 and VGLUT2 in the brain. Subsequently, we will perform structure function studies on VGLUTs in native synapses to identify the underlying molecular interactions. Finally, the little understood VGLUT3 paralog is expressed mainly in subclasses of cholinergic, dopaminergic and GABAergic neurons, but no evidence exists that demonstrates VGLUT3 s role in glutamate release. We will address whether VGLUT3 is used to co-release glutamate with other neurotransmitters, and will test whether presence of glutamate in synaptic vesicles interferes with the storage or release of other neurotransmitters. Our studies will yield important insights into how these transporters operate, and how modulation of VGLUTs affects synaptic encoding and brain function. Because of observed profound regulation of VGLUTs in schizophrenia, depression and Parkinsons disease, these findings will also contribute to diagnosis and treatment of mental illness.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences basic medicine neurology parkinson
- medical and health sciences clinical medicine psychiatry schizophrenia
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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.
ERC-2009-AdG
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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.
Host institution
10117 Berlin
Germany
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.