The synaptic release of glutamate evokes in astrocytes periodic increases in the intracellular calcium concentration ([Ca²⁺]_i), due to activation of metabotropic glutamate receptors (mGluRs). The frequency of these [Ca²⁺]_i oscillations is dynamically controlled by the level of neuronal activity, indicating that they represent a specific, frequency-coded signaling system of neuron-to- astrocyte communication. We recently found that neuronal activity-dependent [Ca²⁺]_i oscillations in astrocytes are the main signal that regulates the coupling between neuronal activity and blood flow, the so-called functional hyperemia. Prostaglandins play a major role in this fundamental phenomenon in brain function, but little is known about a possible link between [Ca²⁺]_i oscillations and prostaglandin release from astrocytes. To investigate whether [Ca²⁺]_i oscillations regulate the release from astrocytes of vasoactive prostaglandins, such as the potent vasodilator prostaglandin E2 (PGE2), we plated wtHEK293 cells - constitutively responding to PGE2 with [Ca²⁺]_i elevations - onto cultured astrocytes, and used them as biosensors of prostaglandin release. After loading the astrocyte-HEK cells co- cultures with the Ca2+ indicator Indo-1, in confocal microscope experiments we found that mGluR-mediated [Ca²⁺]_i oscillations triggered spatially and temporally coordinated [Ca²⁺] _i increases in the sensor cells. This response was absent in a clone of HEK cells unresponsive to PGE2, and recovered after transfection with the InsP3- linked prostanoid receptor EP1. We conclude that [Ca²⁺]_i oscillations in astrocytes regulate prostaglandin releases that retain the oscillatory behaviour of the [Ca²⁺] _i changes. This finely tuned release of PGE2 from astrocytes provides a coherent mechanistic background for the role of these glial cells in functional hyperemia.