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Imaging-inthe-Magnet Report Summary

Project ID: 339513
Funded under: FP7-IDEAS-ERC
Country: France

Mid-Term Report Summary - IMAGING-INTHE-MAGNET (Bridging the gap between cellular imaging and fMRI BOLD imaging)

Part A of the project (Otsu et al., Nat. Neurosci., 2015)
The brain is the most metabolically active tissue in the body; it consists of 2% of the human body’s weight and yet uses 20 % of the body’s energy. Initially, it was assumed that that during brain activation, the increase in blood flow, named functional hyperemia, reflected metabolic consumption and thus the energy demand of activated neurons and glial cells. It is now established that functional hyperemia regulation in fact mostly depends on neurotransmitter signaling, particularly by glutamate, through several mechanisms involving neurons, astrocytes and probably also pericytes and endothelial cells.
The differential weight of these mechanisms remains to be established. In particular, several recent in vivo studies have questioned the role of astrocytes because of the slow and sparse dynamics of their somatic Ca2+ signals and the absence of glutamate metabotropic receptor 5 in adults. Consequently, we re-investigated the role of astrocyte and shown that in anesthetized mice, the physiological release of glutamate in glomeruli, during odor stimulation, reliably triggers Ca2+ increases in astrocyte processes but not in somata. These Ca2+ increases systematically precede the onset of functional hyperemia by 1-2 seconds, re-establishing astrocytes as potential regulators of neurovascular coupling.

Part B of the project (Lyons et al. eLife 2016)
Brain cells need a constant supply of oxygen to fuel their activities. Many studies have previously measured oxygen levels in the brain. However, these studies have looked only roughly and taken measurements from large areas of the brain, or they have involved animals receiving anesthesia, which alters blood flow and oxygen consumption. Recently, chemists have generated new phosphorescent oxygen sensors which emit light at a rate that depends on the local oxygen concentration. Using two-photon excitation and one of these sensors, PtP-C343, we have measured oxygen concentration in the brain of awake unstressed mice. We found that in both the olfactory bulb and the somatosensory cortex of awake, resting mice, the interstitial concentration of oxygen has a mean value of ~23 mm Hg, spanning over a range of about 40 mm Hg. Both brain structures display layer-specific differences and values that are much lower during wakefulness than under isoflurane anesthesia. This work will lead to quantitative investigations of local oxygen consumption in the normal and pathological brain.

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