Alteration of functional connectivity despite preserved cerebral oxygenation during acute hypoxia

Abstract Resting state networks (RSN), which show the connectivity in the brain in the absence of any stimuli, are increasingly important to assess brain function. Here, we investigate the changes in RSN as well as the hemodynamic changes during acute, global hypoxia. Mice were imaged at different levels of oxygen (21, 12, 10 and 8%) over the course of 10 weeks, with hypoxia and normoxia acquisitions interspersed. Simultaneous GCaMP and intrinsic optical imaging allowed tracking of both neuronal and hemodynamic changes. During hypoxic conditions, we found a global increase of both HbO and HbR in the brain. The saturation levels of blood dropped after the onset of hypoxia, but surprisingly climbed back to levels similar to baseline within the 10-min hypoxia period. Neuronal activity also showed a peak at the onset of hypoxia, but dropped back to baseline as well. Despite regaining baseline sO2 levels, changes in neuronal RSN were observed. In particular, the connectivity as measured with GCaMP between anterior and posterior parts of the brain decreased. In contrast, when looking at these same connections with HbO measurements, an increase in connectivity in anterior–posterior brain areas was observed suggesting a potential neurovascular decoupling