An oligodendrocyte (green) immunostained for myelin basic protein (MBP) shown wrapping axons (purple) during the myelination process in vitro.

Impulse activity in axons regulates oligodendrocyte development and myelination at several stages and via different signals. (A) Immature OPCs (NG2+ cells) in white matter on an electrically silent unmyelinated axon. Such cells persist in significant numbers in the adult brain. (B) Electrical activity causes ATP release from axons, which generates adenosine that stimulates differentiation of NG2 cells to a mature oligodendrocyte, and promotes myelination. K+ is released from electrically active axons. Blocking K+ channels in oligodendrocytes in culture has been shown to regulate oligodendrocyte proliferation and lineage progression. (C) Electrical activity can also alter the expression of cell adhesion molecules on the axon that are involved in initiating myelination. This has been shown to regulate myelination by Schwann cells in the PNS, but the same molecule (L1-CAM) is involved in myelination by oligodendrocytes. (D) The release of the neurotransmitters Glu (glutamate) or GABA from synapses formed on NG2 cells, could provide another mechanism to regulate myelination in response to functional activity. (E) After NG2 cells differentiate into oligodendrocytes, ATP released from axons firing action potentials stimulates the synthesis and release of the cytokine LIF from astrocytes, which promotes myelination. Myelination during development and postnatally may be regulated by several other unidentified activity-dependent signaling molecules affecting development of oligodendrocytes and myelin formation. Electrical activity in axons, via the release of neurotransmitters, ions and ATP may influence gene expression in oligodendrocytes by histone modification, RNA transport, local translation and regulate mRNA stability and translation by miRNAs.

A schematic diagram of the axon-oligodendrocyte signaling complex formed at cholesterol-rich microdomains. Fyn kinase is a major integrator of axon-derived signals. The present experiments show that action potential-induced vesicular release of glutamate from axons promotes the formation of cholesterol-rich microdomains, as evidenced by increased trafficking of the transferrin receptor into the membrane, co-localization of the transferrin receptor with phospho-Fyn kinase, increased surface expression of L1CAM, phosphorylation of Fyn kinase, and local translation of MBP, which was dependent on Fyn kinase, after electrical stimulation. These effects are blocked by stimulation when vesicular release from neurons is blocked with BnTX.

Drawings based onpublishedphotomicrographs ofmicroglia in human tissue(adult, except wherelabelled). The top (fromStreit, Walter, & Pennell1999) and bottom (fromMittelbronn et al. 2001)rows are drawn from cellsrevealed using HLA-DR,although the staining andimaging protocols differedproducing different levelsof detail in the originalimages. The middledrawings are frommicroglia revealed usinglectins (from Sheffield,Marquis, & Berman 2000).