Sorting Out Astrocyte Physiology from Pharmacology

A number of exciting findings have been made in astrocytes during the past 15 years that have led many researchers to redefine how the brain works. Astrocytes are now widely regarded as cells that propagate Ca²⁺ over long distances in response to stimulation, and, similar to neurons, release transmitters (called gliotransmitters) in a Ca²⁺-dependent manner to modulate a host of important brain functions. Although these discoveries have been very exciting, it is essential to place them in the proper context of the approaches used to obtain them to determine their relevance to brain physiology. This review revisits the key observations made in astrocytes that greatly impact how they are thought to regulate brain function, including the existence of widespread propagating intercellular Ca²⁺ waves, data suggesting that astrocytes signal to neurons through Ca²⁺-dependent release of glutamate, and evidence for the presence of vesicular machinery for the regulated exocytosis of gliotransmitters.