Imaging-inthe-Magnet · Bridging the gap between cellular imaging and fMRI BOLD imaging

In the brain, blood flow increases locally upon neuronal activation, a response named functional hyperemia. The extent to which functional hyperemia faithfully reports brain activation, spatially or temporally, remains a matter of debate. Solving this question is important, not only because functional hyperemia supplies energy and clears metabolites from activated brain regions, but also because it is used as a proxy to measure brain activation in humans. In particular, the blood-oxygen-level-dependent (BOLD) signal, which is now commonly used for functional magnetic resonance imaging (fMRI), strongly depends on functional hyperemia.Using a combination of standard two-photon imaging and a new one-photon optical development allowing cellular resolution imaging within a fMRI magnet, I will investigate the cellular mechanisms underlying neurovascular coupling and oxygen consumption in the rodent olfactory bulb glomerulus. I will analyze the extent to which these cellular mechanisms are correlated to the BOLD signal, simultaneously acquired during sensory stimulation. The project will focus on the following issues:A. Functional hyperemia: role of neurons and astrocytesHow does functional hyperemia depend on neurons and astrocytes during sensory stimulation? How does it differ in anesthetized and awake animals?B. Oxygen consumption during response to odorHow does the brain’s oxygen partial pressure match neuronal activation and functional hyperemia? How does it differ in anesthetized and awake animals?C. Simultaneous measurements of fMRI BOLD signals, red blood cell flow and cellular responses to odorWhat is the spatial and temporal overlap between the fMRI BOLD signal and i) functional hyperemia at the capillary level, ii) neuron and astrocyte activation and iii) oxygen consumption?