4.7 Article

Properties and Fate of Oligodendrocyte Progenitor Cells in the Corpus Callosum, Motor Cortex, and Piriform Cortex of the Mouse

Journal

JOURNAL OF NEUROSCIENCE
Volume 32, Issue 24, Pages 8173-8185

Publisher

SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0928-12.2012

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Funding

  1. Wellcome Trust
  2. Alzheimer's Society, UK
  3. Bupa Foundation
  4. Medical Research Council
  5. National Health and Medical Research Council [1030939]
  6. National Institutes of Health
  7. European Union (Leukotreat)
  8. MRC [G0800575] Funding Source: UKRI
  9. Medical Research Council [G0800575] Funding Source: researchfish

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Oligodendrocyte progenitor cells (OPCs) in the postnatal mouse corpus callosum (CC) and motor cortex (Ctx) reportedly generate only oligodendrocytes (OLs), whereas those in the piriform cortex may also generate neurons. OPCs have also been subdivided based on their expression of voltage-gated ion channels, ability to respond to neuronal activity, and proliferative state. To determine whether OPCs in the piriform cortex have inherently different physiological properties from those in the CC and Ctx, we studied acute brain slices from postnatal transgenic mice in which GFP expression identifies OL lineage cells. We whole-cell patch clamped GFP-expressing (GFP(+)) cells within the CC, Ctx, and anterior piriform cortex (aPC) and used prelabeling with 5-ethynyl-2'-deoxyuridine (EdU) to assess cell proliferation. After recording, slices were immunolabeled and OPCs were defined by strong expression of NG2. NG2(+) OPCs in the white and gray matter proliferated and coexpressed PDGFR alpha and voltage-gated Na+ channels (I-Na). Approximately 70% of OPCs were capable of generating regenerative depolarizations. In addition to OLIG2(+) NG2(+) I-Na(+) OPCs and OLIG2(+) NG2(neg) I-Na(neg) OLs, we identified cells with low levels of NG2 limited to the soma or the base of some processes. These cells had a significantly reduced INa and a reduced ability to incorporate EdU when compared with OPCs and probably correspond to early differentiating OLs. By combining EdU labeling and lineage tracing using Pdgfr alpha-CreER(T2) : R26R-YFP transgenic mice, we double labeled OPCs and traced their fate in the postnatal brain. These OPCs generated OLs but did not generate neurons in the aPC or elsewhere at any time that we examined.

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