Cerebral oxygenation during locomotion is modulated by respiration

Qingguang Zhang,Serge Charpak,Emmanuelle Chaigneau,William D Haselden,Ravi T Kedarasetti,Patrick J Drew,Kyle W Gheres,Morgane Roche

doi:10.1038/s41467-019-13523-5

Abstract

In the brain, increased neural activity is correlated with increases of cerebral blood flow and tissue oxygenation. However, how cerebral oxygen dynamics are controlled in the behaving animal remains unclear. We investigated to what extent cerebral oxygenation varies during locomotion. 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 find 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 persists when neural activity and functional hyperemia are blocked, occurred both in the tissue and in arteries feeding the brain, and is tightly correlated with respiration rate and the phase of respiration cycle. Thus, breathing rate is a key modulator of cerebral oxygenation and should be monitored during hemodynamic imaging, such as in BOLD fMRI.

Highlights

In the brain, increased neural activity is correlated with increases of cerebral blood flow and tissue oxygenation
When the brain is illuminated with nm light, reflectance decreases report dilations of arteries, capillaries and veins, which correspond with increases in cerebral blood volume (CBV)
Our results show that a short bout of locomotion increases neural activity, which is followed by an increase in CBV and cerebral blood flow (CBF) in FL/HL, and a small decrease or no change in CBV and CBF in frontal cortex (FC)

Summary

Introduction

In the brain, increased neural activity is correlated with increases of cerebral blood flow and tissue oxygenation. A n adequate oxygen supply is critical for proper brain function[1], and deficiencies in tissue oxygen is a noted comorbidity in human diseases[2] and aging[3] For these reasons, there has been a great deal of interest in studying dynamics of cerebral oxygenation[4,5,6,7,8]. Neuromodulator release and neural activity in many brain regions is elevated[11,12,13,14], and there is an increase in cardiac output and respiratory rate How these changes in local and systemic factors interact to control cerebral oxygenation is a fundamental question in brain physiology but is not well understood. Oxygen fluctuations are correlated with spontaneous and locomotion-evoked changes in respiration rate, as well as the phase of the respiration cycle, consistent with a dynamic regulation in systemic oxygenation

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Results

Conclusion