Optical microscopy together with novel imaging probes offers us powerful tools for studying the brain in action and neurovascular coupling in animal models at unprecedented spatio-temporal resolution. In this talk, I will introduce methods that we developed and used for characterizing oxygenation and blood flow changes at rest and in response to functional activation in awake mice across cortical regions and laminar layers, during healthy and diseased conditions. Our results showed that stimulus-induced changes in intravascular partial pressure of O2 (pO2) were conserved across cortical layers, suggesting a tightly controlled neurovascular response to provide adequate O2 supply across cortical depth. I will also discuss the extension of our approach for quantifying oxygenation and blood flow measurements, in two different organs: the eye and the gut. We demonstrated the first examples of quantification of absolute pO2 in the individual capillaries at all three layers of the inner retinal capillary plexus noninvasively through the pupil and in the large intestinal wall of mice by using two-photon microscopy. These developments are opening many possibilities to investigate the concurrent development of microvascular dysfunction in the retina and brain cortex, as well as the progression of intestinal diseases and the role of the gut microbiota.
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