Homeostatic monitoring and control of regional brain blood flow (360G-Wellcome-200893_Z_16_Z)

This research programme is designed to explore cellular and molecular mechanisms underlying homeostatic metabolic control of regional brain blood flow by addressing the following fundamental questions: (Q1) How are the changes in brain parenchymal PCO2/[H+] detected and what are the mechanisms underlying the effect of CO2/H+ on cerebral vasculature? (Q2) What are the mechanisms responsible for hypoxia-induced dilation of cerebral vasculature and what is their role in the redistribution of regional brain blood flow in accord with parenchymal O2 content? (Q3) What is the role of CO2/H+-sensitive mechanisms of astroglial/vascular interface in neuronal activity-dependent control of cerebral vasculature and in generation of the blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) signals? (Q4) What are the cellular identity, sensory transduction mechanism and physiological role of an intracranial baroreceptor capable of sensing decreases in brain perfusion pressure? These questions are addressed by genetic targeting and blockade of hypothesized signalling pathways, in vivo two-photon excitation imaging of neurovascular interface ([Ca2+]i in astrocytes/neurones and parenchymal vasculature) and assessment of regional cerebral blood flow and cerebrovascular reactivity using BOLD and arterial spin labelling fMRI in experimental animals (rats and mice).