Calcium Dynamics in Cortical Astrocytes and Arterioles During Neurovascular Coupling

Abstract

Neuronal activity in the brain is thought to be coupled to cerebral arterioles (functional hyperemia) through Ca 2+ signals in astrocytes. Although functional hyperemia occurs rapidly, within seconds, such rapid signaling has not been demonstrated in situ, and Ca 2+ measurements in parenchymal arterioles are still lacking. Using a laser scanning confocal microscope and fluorescence Ca 2+ 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 2+ waves. Smooth muscle cells in parenchymal arterioles exhibited Ca 2+ and diameter oscillations (“vasomotion”) that were rapidly suppressed by ES. The neuronal-mediated Ca 2+ rise in cortical astrocytes was dependent on intracellular (inositol trisphosphate [IP 3 ]) and extracellular voltage-dependent Ca 2+ channel sources. The Na + channel blocker tetrodotoxin prevented the rise in astrocytic [Ca 2+ ] i and the suppression of Ca 2+ 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 2+ oscillations in parenchymal arterioles. This study supports the concept that astrocytic Ca 2+ changes signal the cerebral microvasculature and indicate the novel concept that this communication occurs through the suppression of arteriolar [Ca 2+ ] i oscillations and corresponding vasomotion. The full text of this article is available online at http://circres.ahajournals.org.