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NG2\u2010glia can generate oligodendrocytes, but it is unlikely this is their only function; indeed, they may be multipotent neural stem cells. Moreover, NG2\u2010glia are a highly reactive cell type and a major function is to help form the axon growth inhibitory glial scar in response to CNS injury. The factors that regulate these diverse behaviours of NG2\u2010glia are not fully resolved, but NG2\u2010glia express receptors to the neurotransmitter glutamate, which has known potent effects on other glia. Here, we have examined the actions of glutamate receptor activation on NG2\u2010glia in the rat optic nerve, a typical CNS white matter tract that does not contain neuronal cell bodies. Glutamate induces an increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> in immuno\u2010identified NG2\u2010glia <jats:italic>in situ<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. In addition, we examined the effects of glutamate receptor activation <jats:italic>in vivo<\/jats:italic> by focal injection of the glutamate receptor agonist kainate into the optic nerve; saline was injected in controls. Changes in glial and axonal function were determined at 7\u00a0days post injection (dpi), by immunohistochemistry and electrophysiological measurement of the compound action potential (CAP). Injection of kainate resulted in a highly localized \u2018injury response\u2019 in NG2\u2010glia, marked by dense labelling for NG2 at the lesion site, as compared to astrocytes, which displayed a more extensive reactive astrogliosis. Furthermore, injection of kainate resulted in an axonal conduction block. These glial and axonal changes were not observed following injection of saline vehicle. In addition, we provide evidence that endogenous glutamate induces calcium\u2010dependent phosphorylation of extracellular signal\u2010regulated kinases (ERK1\/2), which may provide a potential mechanism by which glutamate\u2010mediated changes in raised intracellular calcium could regulate the observed gliosis. The results provide evidence that activation of AMPA\u2010kainate type ionotropic glutamate receptors evoke raised calcium in NG2\u2010glia and induces an injury response in NG2\u2010glia.<\/jats:p>","DOI":"10.1111\/j.1469-7580.2008.01017.x","type":"journal-article","created":{"date-parts":[[2009,1,21]],"date-time":"2009-01-21T13:07:25Z","timestamp":1232543245000},"page":"208-218","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Effects of glutamate receptor activation on NG2\u2010glia in the rat optic nerve"],"prefix":"10.1111","volume":"214","author":[{"given":"Nicola","family":"Hamilton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul S.","family":"Hubbard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur 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