Astrocytic Calcium Signaling: Mechanism and Implications for Functional Brain Imaging

Astrocytes are electrically non-excitable cells that, on a slow time scale of seconds, integrate synaptic transmission by dynamic increases in cytosolic Ca²⁺ . A number of groups have recently shown that astrocytic Ca²⁺ signaling regulates vascular tones and that astrocytes play a central role in functional hyperemia by Ca²⁺ -dependent release of Prostaglandin E2 (PGE₂ ). Astrocytes are, however, not simple detectors of excitatory transmission, since a number of neuromodulator and hormones trigger elevations in astrocytic Ca²⁺ independently of synaptic transmission. Furthermore, astrocytes exhibit ex vivo intrinsic Ca²⁺ excitability, or spontaneous increases in Ca²⁺ that are not triggered by receptor activation. The notion that astrocytes can regulate vascular tone independently of synaptic transmission challenges the notion that changes in the blood oxygenation level dependent (BOLD) signal is directly proportional to neuronal activity and may thus require a reevaluation of the large body of data accumulated using functional magnetic resonance imaging (fMRI).