Table 1 |.

Tools used to study oligodendrocyte and myelin plasticity in rodents

Approach	Advantages	Disadvantages
Tools to impair or prevent new oligodendrocyte differentiation
OPC-specific Cre drivers (such as NG2-CreER or PDGFRα-CreER) to conditionally knock out key genes involved in myelination (creating Myrf cKOs or Olig2 cKOs, for example)	Allows cell type-specific manipulation; onset of impaired differentiation can be controlled by tamoxifen administration	Requires an OPC Cre driver; Myrf or Olig2 may have additional functions beyond regulation of differentiation; effect is not region-specific; does not differentiate between ongoing and experience-induced myelination
Tools to enhance myelination
Clemastine or bazedoxifene	Does not require Cre driver; simple to administer (systemic injection)	Not cell type or region-specific; may have unknown off-target effects
OPC-specific Cre drivers (such as NG2-CreER or PDGFRα-CreER) to conditionally knock out M1R, a negative regulator of myelination (Chrm1 cKO)	Cell type-specific manipulation; onset of enhanced differentiation can be controlled by tamoxifen administration	Requires OPC Cre driver; M1R may have other effects beyond regulating differentiation; effect is not region-specific
Methods to label new oligodendrocyte or myelin formation
Use EdU or BrdU, together with immunostaining for PDGFRa or NG2 (OPCs), CC1 or ASPA (mature oligodendrocytes), or OLIG2 or SOX10 (oligodendrocyte lineage cells)	Does not require Cre driver; identifies OPCs, oligodendrocytes or oligodendrocyte lineage cells that arose from OPCs that proliferated after EdU or BrdU administration	Does not capture oligodendrocytes that directly differentiated without proliferating first; cannot visualize myelin sheaths
OPC-specific Cre drivers (such as NG2-CreER or PDGFRα-CreER) to drive the expression of tau-mGFP	Captures newly formed oligodendrocytes and sheaths that arose from direct differentiation and from OPCs that first proliferated; allows for visualization of myelin sheaths	Requires OPC Cre driver; does not demonstrate the presence of bona fide compact myelin
Expression of fluorescent proteins under the control of OPC-specific promoters (such as NG2-mEGFPorMOBP-EGFP)	Allows for in vivo visualization and tracking of OPCs and differentiated oligodendrocytes; allows for visualization of fine processes in both cell types	Requires in vivo longitudinal imaging to differentiate between existing and newly formed cells; does not demonstrate the presence of bona fide compact myelin

ASPA, aspartoacylase; BrdU, 5-bromo-2′-deoxyuridine; cKO, conditional knockout; EdU, 5-ethynyl-2′-deoxyuridine; OPC, oligodendrocyte precursor cell.