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Content archived on 2024-06-18

Regulation of neuronal connectivity and plasticity by activity-dependent mitochondrial trafficking to synapses

Objective

Regulated trafficking of mitochondria is essential for providing ATP at the correct spatial location to power neural computation, and for providing calcium buffering at sites of calcium entry or release. In neurons, the concentration of mitochondria in specific regions such as growth cones and synapses is important for correct neuronal function and development. Moreover mutations in proteins regulating mitochondrial trafficking compromise neuronal development and the formation, function and plasticity of synapses, and defective mitochondrial trafficking is increasingly implicated in neurological diseases. Understanding the molecular mechanisms that allow neurons to tailor the distribution of mitochondria to changes in neuronal activity therefore has important implications for our understanding of neuronal function and communication. This proposal will study the mechanisms that control the trafficking of the energy providing mitochondria within neurons, and how this relates to neuronal connectivity and plasticity. Using imaging, electrophysiological, molecular and cell biological techniques, combined with viral transduction and mouse transgenic approaches we will determine the molecular mechanisms underlying the activity-dependent subcellular positioning of mitochondria in neurons. We will examine how the mitochondrial Ca2+-sensing GTPases Miro1 and Miro2 act to regulate mitochondrial movement, distribution and function and how this contributes to neuronal development, synaptogenesis and synaptic plasticity. A key goal will be to determine if different roles exist for constitutive versus activity-dependent control of mitochondrial transport by Miro1 and Miro2 in these processes. These studies will significantly advance our understanding of the molecular mechanisms that control mitochondrial localisation in neurons and the role that activity-dependent mitochondrial trafficking plays in regulating neuronal development, morphogenesis, connectivity and function.

Fields of science (EuroSciVoc)

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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.

Call for proposal

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

ERC-2011-StG_20101109
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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.

ERC-SG - ERC Starting Grant

Host institution

UNIVERSITY COLLEGE LONDON
EU contribution
€ 1 997 567,00
Address
GOWER STREET
WC1E 6BT LONDON
United Kingdom

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Region
London Inner London — West Camden and City of London
Activity type
Higher or Secondary Education Establishments
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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.

No data

Beneficiaries (1)

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