Quantifying the structure function of the neurovascular interface from micro ci...
Quantifying the structure function of the neurovascular interface from micro circuits to large scale functional organization
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 activ...
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.ver más
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