Oligodendrocyte precursor cells (OPCs) have become the focus of intense research, not only because they generate myelin-forming oligodendrocytes in the normal CNS, but because they may be suitable for transplantation to treat disorders in which myelin does not form or is damaged, and because they have stem-cell-like properties in that they can generate astrocytes and neurons as well as oligodendrocytes. In this article we review the electrical signalling properties of OPCs, including the synaptic inputs they receive and their use of voltage-gated channels to generate action potentials, and we describe experiments attempting to detect output signalling from OPCs. We discuss controversy over the existence of different classes of OPC with different electrical signalling properties, and speculate on the lineage relationship and myelination potential of these different classes of OPC. Finally, we point out that, since OPCs are the main proliferating cell type in the mature brain, the discovery that they can develop into neurons raises the question of whether more neurons are generated in the mature brain from the classical sites of neurogenesis in the subventricular zone of the lateral ventricle and the hippocampal dentate gyrus or from the far more widely distributed OPCs.

NG2-glia are a distinct class of CNS glial cells that are generally classed as oligodendrocyte progenitor cells. However, in the adult CNS a large fraction of NG2 cells does not appear to divide or generate oligodendrocytes. The functions of these adult NG2-glia, which we have termed synantocytes, are unknown. NG2-glia (synantocytes) form interactive domains with astrocytes and neurons. Within their domains, NG2-glia and astrocytes contact the same neurons, form multiple heterologous contacts with each other, and contact pericytes which regulate cerebral blood flow. NG2-glia receive presynaptic input from neurons and respond to neurotransmitters released at synapses. In addition, NG2-glia are intimately associated with astroglia and respond to astroglial signals, a hitherto neglected aspect of NG2-glial cell physiology. The non-overlapping domain organisation of astrocytes is believed to be important in isolating and integrating activity at the synapses and blood vessels within their domains. The domains of NG2-glia overlap with astrocytes, suggesting they could play a role in integrating non-overlapping astrocyte domains.

NG2 cells represent a unique glial cell population that is distributed widely throughout the developing and adult CNS and is distinct from astrocytes, mature oligodendrocytes and microglia. The ability of NG2 cells to differentiate into myelinating oligodendrocytes has been documented in vivo and in vitro. We reported recently that NG2 cells in the forebrain differentiate into myelinating oligodendrocytes but into a subpopulation of protoplasmic astrocytes (Zhu et al., 2008). However, the in vivo fate of NG2 cells in the spinal cord and cerebellum has remained unknown. To investigate the fate of NG2 cells in caudal central nervous system (CNS) regions in vivo, we examined the phenotype of cells that express EGFP in mice that are double transgenic for NG2CreBAC and the Cre reporter Z/EG. The fate of NG2 cells can be studied in these mice by permanent expression of EGFP in cells that have undergone Cre-mediated recombination in NG2 cells. We find that NG2 cells give rise to oligodendrocytes in both gray and white matter of the spinal cord and cerebellum, and to protoplasmic astrocytes in the gray matter of the spinal cord. However, NG2 cells do not give rise to astrocytes in the white matter of the spinal cord and cerebellum. These observations indicate that NG2 cells serve as precursor cells for oligodendrocytes and a subpopulation of protoplasmic astrocytes throughout the rostrocaudal axis of the CNS.