Calcium Dynamics in Cortical Astrocytes and Arterioles During Neurovascular Coupling

Neuronal activity in the brain is thought to be coupled to cerebral arterioles (functional hyperemia) through Ca signals in astrocytes. Although functional hyperemia occurs rapidly, within seconds, such rapid signaling has not been demonstrated in situ, and Ca measurements in parenchymal arterioles are still lacking. Using a laser scanning confocal microscope and fluorescence Ca indicators, we provide the first evidence that in a brain slice preparation, increased neuronal activity by electrical stimulation (ES) is rapidly signaled, within seconds, to cerebral arterioles and is associated with astrocytic Ca waves. Smooth muscle cells in parenchymal arterioles exhibited Ca and diameter oscillations (“vasomotion”) that were rapidly suppressed by ES. The neuronal-mediated Ca rise in cortical astrocytes was dependent on intracellular (inositol trisphosphate [IP3]) and extracellular voltage-dependent Ca channel sources. The Na channel blocker tetrodotoxin prevented the rise in astrocytic [Ca]i and the suppression of Ca oscillations in parenchymal arterioles to ES, indicating that neuronal activity was necessary for both events. Activation of metabotropic glutamate receptors in astrocytes significantly decreased the frequency of Ca oscillations in parenchymal arterioles. This study supports the concept that astrocytic Ca changes signal the cerebral microvasculature and indicate the novel concept that this communication occurs through the suppression of arteriolar [Ca]i oscillations and corresponding vasomotion. The full text of this article is available online at http://circres.ahajournals.org.