Imaging local neuronal activity by monitoring PO₂ transients in capillaries

Two-photon phosphorescence lifetime microscopy (2PLM) has been used recently for depth measurements of oxygen partial pressure (PO(2)) in the rodent brain. In capillaries of olfactory bulb glomeruli, 2PLM has also allowed simultaneous measurements of PO(2) and blood flow and revealed the presence of erythrocyte-associated transients (EATs), which are PO(2) 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, PO(2) at EAT peaks overestimates the mean PO(2) by 35 mm Hg. PO(2) between two EAT peaks is at equilibrium with, and thus reports, PO(2) in the neuropil. During odor stimulation, there is a small PO(2) decrease before functional hyperemia, showing that the initial dip in PO(2) 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.