The highly integrated dialogue between neurons and astrocytes in brain function.

For decades neurons have been regarded as the only cells involved in the generation and control of brain signalling, while the surrounding glia was supposed to provide structural and metabolic support to neuronal function. However, based on a number of recent findings, a new view is emerging: astrocytes, the glial cells ensheathing synaptic specializations, are active and integrated participants of neurotransmission. Not only do astrocytes take up and remove synaptically released glutamate (the major excitatory neurotransmitter), thus ending its stimulatory action and preventing neuronal damage, but also and outstandingly, they are able to undergo rapid bidirectional communication with neurons, based on reciprocal glutamatergic signalling. Thus, release of glutamate from synaptic terminals, in addition to postsynaptic neurons, turns on the astrocytes nearby which respond by liberating the same neurotransmitter via a novel Ca(2+)-dependent mechanism and thereby signal back to neurons. The present review discusses the above findings and their important implications as well as additional evidence supporting the new concept of an integrated neuron-astrocyte communication in brain function.