In the brain, increased neural activity is correlated with an increase of cerebral blood flow and increased tissue oxygenation. However, how cerebral oxygen dynamics are controlled in the behaving animals remains unclear. Here, we investigated to what extent the cerebral oxygenation varies during natural behaviors that change the whole-body homeostasis, specifically exercise. We measured oxygen levels in the cortex of awake, head-fixed mice during locomotion using polarography, spectroscopy, and two-photon phosphorescence lifetime measurements of oxygen sensors. We found that locomotion significantly and globally increases cerebral oxygenation, specifically in areas involved in locomotion, as well as in the frontal cortex and the olfactory bulb. The oxygenation increase persisted when neural activity and functional hyperemia were blocked, occurred both in the tissue and in arteries feeding the brain, and was tightly correlated with respiration rate and the phase of respiration cycle. Thus, respiration provides a dynamic pathway for modulating cerebral oxygenation.

Cerebral oxygenation during locomotion is modulated by respiration