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.
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Acknowledgements
We thank S. Vinogradov (Department of Biochemistry and Biophysics, University of Pennsylvania) for providing PtP-C343 through the intermediate of Oxygen Enterprises. We also thank G. Bouchery and A. Virolle for help in animal surgery, S. Sasnouski for software improvements and M. Ducros, B. Weber and U. Lindauer for critical comments. Support was provided by INSERM, CNRS, the Leducq Foundation, the Human Frontier Science Program Organization (HSFPO), the Agence Nationale de la Recherche and the Fondation pour la Recherche Médicale.
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A.P., Y.G.H. and S.C. conducted the experiments and analyzed the data. All authors edited the paper.
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Parpaleix, A., Houssen, Y. & Charpak, S. Imaging local neuronal activity by monitoring PO2 transients in capillaries. Nat Med 19, 241–246 (2013). https://doi.org/10.1038/nm.3059
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DOI: https://doi.org/10.1038/nm.3059
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