Lay summary
We discovered a novel baroreceptor located inside the brain - ‘intra-cranial’ that senses physiological changes in cerebral blood pressure. Traditionally, ‘peripheral’ baroreceptors in the carotid sinus/aortic arch modulate heart rate and vascular resistance via autonomic nerves. However, when brain blood flow decreases, intra-cranial baroreceptors are activated causing increases in nerve activity to raise arterial pressure, thereby restoring brain blood flow; this has been demonstrated in rats under anaesthesia. We hypothesise that this mechanism also operates in conscious rats, is essential for setting levels of basal arterial pressure and is sensitized in hypertension. Through iteration between a new mathematical model and physiological studies in conscious rats, we will determine: (i) interactions between intra-cranial and peripheral baroreceptors; (ii) if astrocytic signaling is key for intra-cranial baroreceptor function, and (iii) mechanisms of sensory transduction of intra-cranial baroreceptors. Revealing these novel mechanisms will inform future management of hypertension, which affects ~30% of Aotearoa’s population.