Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation

The cellular mechanisms underlying functional hyperemia-the coupling of neuronal activation to cerebral blood vessel responses-are not yet known. Here we show in rat cortical slices that the dilation of arterioles triggered by neuronal activity is dependent on glutamate-mediated [Ca2+](i) oscillations in astrocytes. Inhibition of these Ca2+ responses resulted in the impairment of activity-dependent vasodilation, whereas selective activation-by patch pipette-of single astrocytes that were in contact with arterioles triggered vessel relaxation. We also found that a cyclooxygenase product is centrally involved in this astrocyte-mediated control of arterioles. In vivo blockade of glutamate-mediated [Ca2+](i) elevations in astrocytes reduced the blood flow increase in the somatosensory cortex during contralateral forepaw stimulation. Taken together, our findings show that neuron-to-astrocyte signaling is a key mechanism in functional hyperemia.