Skip to main content

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

Periodic Reporting for period 3 - MultiScaleNeurovasc (Quantifying the structure-function of the neurovascular interface: from micro-circuits to large-scale functional organization)

Reporting period: 2018-06-01 to 2019-11-30

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 activity 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.
In this project, we seek to unveil the underplaying structural and functional organization and links between neurons and blood vessels in the brain. A clear understanding of this intricate interface will allow us to better decipher human functional imaging experiments as well as prevent and treat neurodegenerative disease liked to malfunctions of the brain vasculature.
There two overarching goals in this project: first to map across different brain scales the structural organization of this interface and second, to understand, at the cellular level and across large neuronal populations, how neuronal network activity is translated into a vascular output (this is the core of the neurovascular transform function).
Towards these goals, I have established a team of multidisciplinary students and staff scientist from backgrounds in the fields of biology, physics and electrical engineering. All work together at different aspects of the project as we face interesting challenges along the way. For example, we while most imaging in the neurophysiology is done on a single (or multiple planes, one at the time) we seek here to develop fast volumetric imaging to obtain the most relevant vascular and neuronal dynamics, in doing so we had to develop novel electronics to account for the decreasing number of photons available as one moves faster across the sample (as it happens in volumetric imaging).
As part of the work in this project, we have recently discovered that, despite working together, the vasculature around neuronal ensembles across different mouse brain regions that convey sensory information from the outside world to the brain, does not line up with these neuronal units. It seems like the solution to this apparent conundrum lies in the fine details of the neuronal-vascular microcircuity (i.e. understanding how single neuronal processes signal to the nearby vasculature). We are currently working to decipher this complex structural organization while mapping also the distribution of the cellular signaling machinery. We expect that once completed, this mapping will represent one of the most significant contributions of this project as we will have quantitatively defined a novel neuroscience concept: the neuro-glio-vascular synapse.