Artifact versus reality--how astrocytes contribute to synaptic events

The neuronal doctrine, developed a century ago regards neuronal networks as the sole substrate of higher brain function. Recent advances in glial physiology have promoted an alternative hypothesis, which places information processing in the brain into integrated neuronal-glial networks utilizing both binary (neuronal action potentials) and analogue (diffusional propagation of second messengers/metabolites through gap junctions or transmitters through the interstitial space) signal encoding. It has been proposed that the feed-forward and feed-back communication between these two types of neural cells, which underlies information transfer and processing, is accomplished by the release of neurotransmitters from neuronal terminals as well as from astroglial processes. Understanding of this subject, however, remains incomplete and important questions and controversies require resolution. Here we propose that the primary function of perisynaptic glial processes is to create an "astroglial cradle" that shields the synapse from a multitude of extrasynaptic signaling events and provides for multifaceted support and long-term plasticity of synaptic contacts through variety of mechanisms, which may not necessarily involve the release of "glio" transmitters.