D-serine signalling in the brain: friend and foe

Neurons and glia talk to each other at synapses. Glia sense the level of synaptic activity and consequently regulate its efficacy via the release of neuromodulators. One such glia-derived modulator is D-serine, an amino acid that serves as an endogenous ligand for the strychnine-insensitive glycine-binding site of NMDA glutamate receptors. Here, we provide an overview of recent findings on the mechanisms of its synthesis, release and clearance at synapses, with an emphasis on the dichotomy of behaviour of this novel messenger in the brain. The discovery of the good and ugly faces of this glio-transmitter is an important issue of modern neuroscience that has repercussions for the treatment of brain disorders.