Johns Hopkins scientists have discovered to their
surprise that nerves in the mammalian brain's white matter
do more than just ferry information between different brain
regions; they, in fact, process information the way gray
matter cells do.
The discovery in mouse cells, outlined in the cover
story of the March issue of Nature Neuroscience,
shows that brain cells "talk" with each other in more ways
than previously thought.
"We were surprised to see these nerve axons talking to
other cells in the white matter," said Dwight Bergles, an
associate professor of
neuroscience in the School of
Medicine.
The discovery focuses on oligodendrocyte precursor
cells, or OPCs, whose main role when they mature into
oligodendrocytes is to wrap themselves around and insulate
nerves with a whitish coat of protective myelin. The
immature cells simply hang around and divide very slowly,
waiting to be spurred into action.
To learn more about OPCs that reside in the brain's
white matter, the Johns Hopkins researchers measured
activity from individual precursor cells in the corpus
callosum, a region of white matter that connects the two
brain hemispheres. To their surprise, OPCs were found to
have electrical signals produced by the neurotransmitter
glutamate, similar to the signals used as the principal
means of cell-to-cell communication and information
processing in the gray matter. The phenomenon was unlikely,
they said, because in the mouse brain, OPCs in the
myelin-rich white matter are far from synapses, the points
of contact between nerves where glutamate is released.
Theorizing that OPCs might have experienced glutamate
in some less obvious way in this area of the brain, Bergles
and his team studied nearby nerve cells to figure out where
the glutamate might be coming from.
By forcing single nerve cells to become excited one at
a time, they discovered that as electrical impulses are
carried along the nerves, glutamate is released and causes
electrical signals in the OPCs. A further microscopic hunt
revealed that pools of glutamate were present in the nerve
fibers wherever they touched OPCs. All of the nerve cells in
the white matter that released glutamate within reach of
OPCs, moreover, had something in common: no myelin
insulation.
Normally myelin speeds electrical impulses. Cells
lacking the coating fire 20 to 90 times more slowly than
cells coated with myelin. Myelin loss is well-known to
impair signaling and information processing, causing nerve
cells to die and creating such neurodegenerative conditions
as multiple sclerosis.
Bergles speculates that this white matter activity his
team discovered may help "naked" nerve cells signal nearby
OPCs and say "cover me with myelin because we need to
replace another cell that has been damaged."
The research was funded by the National Institutes of
Health, March of Dimes, NARSAD, National Multiple Sclerosis
Society and Medical Scientist Training Program.
Authors on the paper are Jennifer Ziskin and Bergles,
both of Johns Hopkins; Akiko Nishiyama and Maria Rubio, of
the University of Connecticut; and Masahiro Fukaya, of
Hokkaido University in Sapporo, Japan.