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Quantifying the structure-function of the neurovascular interface: from micro-circuits to large-scale functional organization

Objective

Neuronal computations in the brain require a high metabolic budget yet the brain has extremely limited resources; calling for an on-demand, robust supply system to deliver nutrients to active regions. In most cases, neuronal activity results in an increase in blood flow to the active area, a phenomenon called functional hyperaemia. This coupling between neuronal and vascular activtuy underpins the mechanism enabling fMRI to map neuronal activity based on vascular dynamics; further, malfunction of the cellular players involved in coupling is now considered to play a key role in otherwise classically defined neurodegenerative diseases. We lack a concise description of the inner workings of this mechanism and a thorough quantitative description of the neuro-gila-vascular interface; issues that are best addressed by an investigation into the cellular mechanisms, the temporal dynamics and multi-scale spatial organization governing neurovascular coupling. My long-term goal is to provide a unified theory to encapsulate our knowledge on neurovascular coupling. Here, I hypothesize that functional hyperaemia results from the constant integration of vasoactive cues with region-dependent coupling emerging from different neuro-glia-vascular microcircuits, nuances in afferent wiring into vascular contractile elements and/or neuronal activity patterns. I will test this hypothesis with a multi-faceted correlative approach combining: two-photon awake imaging of cellular and vascular dynamics to obtain physiological data unaffected by anaesthetics; super-resolution structural imaging of intact volumes to map the fine details of micro-circuit structure; array-tomography to map in situ the neurovascular signalling machinery and novel optogenic tools to manipulate several of its specific components. I expect to offer a revolutionary mechanistic insight into one of the most basic and fundamental physiological processes behind the structure and function of the brain.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2014-STG

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Host institution

TEL AVIV UNIVERSITY
Net EU contribution

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.

€ 1 500 000,00
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.

€ 1 500 000,00

Beneficiaries (1)

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