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

Abstract

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 ϩ ) cells within the CC, Ctx, and anterior piriform cortex (aPC) and used prelabeling with 5-ethynyl-2Ј-deoxyuridine (EdU) to assess cell proliferation. After recording, slices were immunolabeled and OPCs were defined by strong expression of NG2. NG2ϩ OPCs in the white and gray matter proliferated and coexpressed PDGFR␣ and voltage-gated Na ϩ channels (I Na ). Approximately 70% of OPCs were capable of generating regenerative depolarizations. In addition to OLIG2 ϩ NG2 ϩ I Na ϩ OPCs and OLIG2 ϩ 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 I Na 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␣-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.

Oligodendrocyte Development and Plasticity

“…Nevertheless, there has been a recent report that OPCs can produce new neurons in the adult hypothalamus (Robins et al 2013), potentially contributing to the function of circuits that control body homeostasis (e.g., appetite and satiety). Previous reports that OPCs might generate small numbers of new projection neurons in the adult piriform cortex (olfactory cortex) (Rivers et al 2008;Guo et al 2010) were not substantiated subsequently (Kang et al 2010;Clarke et al 2012).…”

“…It is not known whether this is because the dorsal and ventral lineages are intrinsically specialized for different tasks or the dorsal cells are generated slightly later during development and, hence, remain more "youthful" and better able to compete for limiting mitogens or other extracellular signals. It has, so far, not been possible to distinguish dorsally and ventrally derived OPCs by their antigenic or electrophysiological properties Clarke et al 2012). Ultimately, genome-wide screens of expressed genes (e.g., by RNA sequencing) in purified populations of dorsal versus ventral OL lineage cells might determine whether different OL subtypes are linked to their developmental origins.…”

Spatiotemporally different origins of NG2 progenitors produce cortical interneurons versus glia in the mammalian forebrain

“…The important role of these spatially and temporally specific regulatory processes is further supported by the fact that different postnatal NG2 + ;PDGFαR + progenitor pools have diverse lineage outcomes ( Fig. 5) and electrophysiological properties (15,(31)(32)(33).…”

Exercise training for neural recovery in a restricted sample of pediatric brain tumor survivors: a controlled clinical trial with crossover of training versus no training

“…21,22 Notably, white matter tracts and the hippocampus-structures most affected by radiation-are niches for neural precursor cells. 23,24 We conducted a clinical trial of exercise training in survivors of pediatric brain tumors treated with cranial radiation. Our primary objective was to test whether exercise training leads to changes in brain structure.…”