An oligodendrocyte

(green) immunostained for myelin basic protein (MBP) shown wrapping axons (purple)
during the myelination process in vitro.
Impu
lse activity in axons regulates oligodendrocyte development and myelination at several stages
and via different signals. (A) Immature OPCs (NG2 cells) in !"ite matter on an electrically
silent unmyelinated axon. #uc" cells persist in significant num$ers in t"e adult $rain. (%)
&lectrical activity causes A'P release from axons( !"ic" generates adenosine t"at stimulates
differentiation of NG2 cells to a mature oligodendrocyte( and promotes myelination. ) is
released from electrically active axons. %loc*ing ) c"annels in oligodendrocytes in culture "as
$een s"o!n to regulate oligodendrocyte proliferation and lineage progression. (C) &lectrical
activity can also alter t"e expression of cell ad"esion molecules on t"e axon t"at are involved in
initiating myelination. '"is "as $een s"o!n to regulate myelination $y #c"!ann cells in t"e
PN#( $ut t"e same molecule (+,-CA.) is involved in myelination $y oligodendrocytes. (/) '"e
release of t"e neurotransmitters Glu (glutamate) or GA%A from synapses formed on NG2 cells(
could provide anot"er mec"anism to regulate myelination in response to functional activity. (&)
After NG2 cells differentiate into oligodendrocytes( A'P released from axons firing action
potentials stimulates t"e synt"esis and release of t"e cyto*ine +I0 from astrocytes( !"ic"
promotes myelination. .yelination during development and postnatally may $e regulated $y
several ot"er unidentified activity-dependent signaling molecules affecting development of
oligodendrocytes and myelin formation. &lectrical activity in axons( via t"e release of
neurotransmitters( ions and A'P may influence gene expression in oligodendrocytes $y "istone
modification( 1NA transport( local translation and regulate m1NA sta$ility and translation $y
mi1NAs.
A sc"ematic diagram of
t"e axon-oligodendrocyte signaling complex formed at c"olesterol-ric" microdomains. 0yn
*inase is a ma2or integrator of axon-derived signals. '"e present experiments s"o! t"at action
potential-induced vesicular release of glutamate from axons promotes t"e formation of
c"olesterol-ric" microdomains( as evidenced $y increased traffic*ing of t"e transferrin receptor
into t"e mem$rane( co-locali3ation of t"e transferrin receptor !it" p"osp"o-0yn *inase(
increased surface expression of +,CA.( p"osp"orylation of 0yn *inase( and local translation of
.%P( !"ic" !as dependent on 0yn *inase( after electrical stimulation. '"ese effects are
$loc*ed $y stimulation !"en vesicular release from neurons is $loc*ed !it" %n'4.
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).