The oxygen initial dip in the brain of anesthetized and awake mice

Proc Natl Acad Sci U S A. 2022 Apr 5;119(14):e2200205119. doi: 10.1073/pnas.2200205119. Epub 2022 Mar 30.


An ongoing controversy in brain metabolism is whether increases in neural activity cause a local and rapid decrease in oxygen concentration (i.e., the “initial dip”) preceding functional hyperemia. This initial dip has been suggested to cause a transient increase in vascular deoxyhemoglobin with several imaging techniques and stimulation paradigms, but not consistently. Here, we investigate contributors to this initial dip in a distinct neuronal network, an olfactory bulb (OB) glomerulus most sensitive to a specific odorant (ethyl tiglate [ET]) and a site of strong activation and energy consumption upon ET stimulation. Combining two-photon fluorescence and phosphorescence lifetime microscopy, and calcium, blood flow, and pO2 measurements, we characterized this initial dip in pO2 in mice chronically implanted with a glass cranial window, during both awake and anesthetized conditions. In anesthetized mice, a transient dip in vascular pO2 was detected in this glomerulus when functional hyperemia was slightly delayed, but its amplitude was minute (0.3 SD of resting baseline). This vascular pO2 dip was not observed in other glomeruli responding nonspecifically to ET, and it was poorly influenced by resting pO2. In awake mice, the dip in pO2 was absent in capillaries as well as, surprisingly, in the neuropil. These high-resolution pO2 measurements demonstrate that in awake mice recovered from brain surgery, neurovascular coupling was too fast and efficient to reveal an initial dip in pO2.

Keywords: initial dip; neurovascular coupling; oxygen.

MeSH terms

  • Animals
  • Brain* / blood supply
  • Brain* / metabolism
  • Mice
  • Nerve Net
  • Neurons / physiology
  • Neurovascular Coupling*
  • Olfactory Bulb / metabolism
  • Oxygen* / metabolism
  • Wakefulness*


  • Oxygen