Classic studies have recognized neurons and three glial elements in the central nervous system (CNS) -astrocytes, oligodendrocytes and microglia. The identification of novel glia that specifically express the NG2 chondroitin sulphate proteoglycan (CSPG) raises the possibility of a fifth element. Until recently, all NG2-expressing glia were considered to be oligodendrocyte precursor cells (OPCs) that persist in the adult CNS to generate oligodendrocytes throughout life. However, this narrow view of the function of 'NG2-glia' is being challenged. The majority of NG2-expressing glia in the adult CNS are a distinct class of cells that we have called 'synantocytes' (from the Greek synanto for contact). Synantocytes are stellate cells, with large process arborizations, and are exquisitely related to neurons. Individual cells traverse white and grey matter and form multiple contacts with neurons, astrocytes, oligodendrocytes and myelin. Synantocytes are an integral component of the 'tetrapartite' synapse, and provide a potential integrative neuron-glial communications pathway. Neuronal activity, glutamate and adenosine triphosphate (ATP) act on synantocyte receptors and evoke raised intracellular calcium. It remains to be seen whether this serves a physiological function, but synantocytes may be specialized to monitor signals from neurons and glia, and to respond to changes in the integrity of the CNS via their specific contacts and ion channel and receptor profiles. The general consequences of synantocyte activation are proliferation and phenotypic changes, resulting in glial scar formation, or regeneration of oligodendrocytes, and possibly neurons.

Models of central nervous system (CNS) function have historically been based on neurons and their synaptic contacts -the neuronal doctrine. This doctrine envisages glia as passive supportive cells. However, electrophysiological and imaging studies in brain slices show us that astrocytes, the most numerous cells in the brain, express a wide range of neurotransmitter receptors that are activated in response to synaptic activity. Furthermore, astrocytes communicate via calcium signals that are propagated over long distances by the release of 'gliotransmitters', the most abundant being adenosine triphosphate (ATP). This has led to the concept of the neuron-astroglial functional unit as the substrate of integration in the CNS. Recently, a novel glial cell type has been characterized by expression of the proteoglycan NG2. These NG2-glia receive presynaptic input from neurons and responds to neurotransmitters released at synapses. Now, studies on transgenic mice in which fluorescent proteins are specifically expressed by subclasses of glia are helping to address the question of where NG2-glia fit in the neuron-astroglial model of integrated brain function. NG2-glia, as well as astrocytes, have been shown to respond to neuronal and astroglial signals by raised intracellular calcium, which is a potential communications mechanism by which NG2-glia may be active partners in neuron-glial circuits. Moreover, a current concept of NG2-glia considers them to be 'neural stem cells' and an exciting prospect is that neuron-glial signalling may regulate the differentiation capacity of NG2-glia and their response to injury.