Is neuronal communication with NG2 cells synaptic or extrasynaptic?

NG2-expressing glial cells (NG2 cells) represent a major pool of progenitors able to generate myelinating oligodendrocytes, and perhaps astrocytes and neurones, in the postnatal brain. In the last decade, it has been demonstrated that NG2 cells receive functional glutamatergic and GABAergic synapses mediating fast synaptic transmission in different brain regions. However, several controversies exist in this field. While two classes of NG2 cells have been defined by the presence or absence of Na(+) channels, action potential firing and neuronal input, other studies suggest that all NG2 cells possess Na(+) conductances and are the target of quantal neuronal release, but are unable to trigger action potential firing. Here we bring new evidence supporting the idea that the level of expression of Na(+) conductances is not a criterion to discriminate NG2 cell subpopulations in the somatosensory cortex. Surprisingly, recent reports demonstrated that NG2 cells detect quantal glutamate release from unmyelinated axons in white matter regions. Yet, it is difficult from these studies to establish whether axonal vesicular release in white matter occurs at genuine synaptic junctions or at ectopic release sites. In addition, we recently reported a new mode of extrasynaptic communication between neurones and NG2 cells that relies on pure GABA spillover and does not require GABAergic synaptic input. This review discusses the properties of quantal neuronal release onto NG2 cells and gives an extended overview of potential extrasynaptic modes of transmission, from ectopic to diffuse volume transmission, between neurones and NG2 cells in the brain.