Imaging local neuronal activity by monitoring PO2 transients in capillaries

Abstract
Two-photon phosphorescence lifetime microscopy (2PLM) has been used recently for depth measurements of oxygen partial pressure (PO2) in the rodent brain. In capillaries of olfactory bulb glomeruli, 2PLM has also allowed simultaneous measurements of PO2 and blood flow and revealed the presence of erythrocyte-associated transients (EATs), which are PO2 gradients that are associated with individual erythrocytes. We investigated the extent to which EAT properties in capillaries report local neuronal activity. We find that at rest, PO2 at EAT peaks overestimates the mean PO2 by 35 mm Hg. PO2 between two EAT peaks is at equilibrium with, and thus reports, PO2 in the neuropil. During odor stimulation, there is a small PO2 decrease before functional hyperemia, showing that the initial dip in PO2 is present at the level of capillaries. We conclude that imaging oxygen dynamics in capillaries provides a unique and noninvasive approach to map neuronal activity.