In this article we refer to both the perinatal and adult cells as NG2-glia. The sheer number of NG2-glia in the adult brain and their uniform distribution in both gray and white matter seemed counterintuitive. Given their presumed role as oligodendrocyte

precursors, should they not be concentrated in white matter where they would presumably be in most demand for myelinating axons? Why should so many precursor cells persist in the mature adult brain in any case? Moreover, the complex process-bearing morphology of NG2-glia in vivo seemed more in keeping with differentiated cells than immature precursors. Perhaps NG2-glia served a dual purpose—as a source of oligodendrocytes during development but fulfilling some more homeostatic or “functional” role in the adult (Nishiyama et al., 1999, Butt et al., ISRIB in vivo 2002, Wigley et al., 2007 and Nishiyama et al., 2009). Anatomical studies revealed that NG2-glia form close contacts with neurons—with axons at nodes of Ranvier and in close proximity to synapses at neuronal cell bodies (Butt et al., 1999, Butt et al., 2002 and Wigley and Butt, 2009).

The hypothesis was born that NG2-glia, or a subset of them, might be involved in some aspects of information processing, in partnership with neurons. This idea took off—and NG2-glia became really “exciting”—when electrophysiologists weighed in. It was already known that NG2-glia express some ion channels and neurotransmitter receptors and that glutamate can influence their proliferation and differentiation in culture http://www.selleckchem.com/products/abt-199.html (Barres et al., 1990, Patneau et al., 1994 and Gallo et al., 1996). However, the first demonstration that NG2-glia in the hippocampus receive long-range synaptic input from neurons in vivo sent waves through the research community (Bergles et al., 2000). Synaptic communication between neurons and NG2-glia, both glutamatergic and GABAergic, was subsequently demonstrated in the cerebellum and cerebral cortex, both in gray and white matter (Lin and Bergles, 2002, Chittajallu et al., 2004, Káradóttir et al., 2005, Lin et al., 2005, Salter and Fern, 2005, Paukert and Bergles,

2006, Kukley et al., 2007, Ziskin et al., 2007 and Hamilton et al., 2009). Physical synapses were identified between NG2 glia and unmyelinated axons in the corpus Ketanserin callosum (Kukley et al., 2007 and Ziskin et al., 2007). Some NG2-glia were found to display spiking sodium currents in response to an initial depolarization (Chittajallu et al., 2004, Káradóttir et al., 2008, Mangin et al., 2008 and De Biase et al., 2010). Suddenly, NG2-glia appeared exotic, ambiguous—glial in form (since they do not possess axons) but with some electrical properties akin to neurons. Their chimeric nature also contributed to the idea that NG2-glia, in their “other” role as precursor cells, might be more malleable than previously imagined and perhaps capable of transforming into neurons as well as glia. One study in particular launched the idea of NG2-glia as latent neural stem cells.