Oct 17, 2014
Researchers have discovered that oligodendrocytes play an active role in learning motor tasks. Rodents whose oligodendrocyte precursor cells were blocked from maturation were unable to acquire a novel motor skill.
Researchers have discovered that oligodendrocytes play an active role in learning motor tasks. Rodents whose oligodendrocyte precursor cells were blocked from maturation were unable to acquire a novel motor skill.
CYNTHIA MCKELVEY
When neuroscientists talk about the process of learning, they usually discuss neurons sprouting new connections, or beefing up the ones they already have. Glia, it has long seemed, are passive bystanders. But new research published this week in Science(McKenzie et al., 2014) suggests that glia, specifically oligodendrocytes, play an active role in the learning of a new motor skill.
Using a method to block the maturation of oligodendrocyte precursor cells (OPCs) without affecting existing oligodendrocytes or myelin, researchers tested the ability of mice to pick up a novel motor task—in this case, running on a wheel with irregularly spaced rungs. Mice whose OPCs were prevented from maturing had a more difficult time learning the task. If the mice were allowed to learn the task before receiving the OPC maturation block, they were able to recall the running strategy with no problems.
The data suggest that functioning, mature oligodendrocytes are critical players in acquiring new motor-based skills. This study and others may also add some pieces to the puzzle of maturational arrest of OPCs in patients with MS.
The study
The researchers targeted myelin regulatory factor (MyRF), a transcription factor that is only expressed in oligodendrocytes and is critical for initiating myelination. Using tamoxifen—a drug typically used to treat breast cancer but also used to modulate gene expression in mice—the researchers inactivated the MyRF allele in the OPCs of mice, preventing them from maturing into oligodendrocytes. The treatment did not affect preexisting oligodendrocytes or myelin.
The researchers then allowed the mice to learn to use the complex wheel. The complex wheel is modified from a regular running wheel by removing rungs at random intervals. Normally, wild-type mice take approximately a week to develop an effective strategy to use the wheel.
“When a normal mouse runs on a normal wheel, what it does is it reaches forward with its left front paw, and then it brings its left rear paw up and grabs the rung immediately behind its front paw,” said the study’s corresponding author, Bill Richardson, Ph.D., of University College London, in an interview with MSDF. But when the mouse runs on the complex wheel and brings its hind paw forward, the rung might not be there. “They very quickly learn to adapt and they grab the same rung as their forepaw. They learn general strategies, they don’t just memorize the pattern,” Richardson said.
[This video begins with a wild-type mouse on its first introduction to the complex wheel. Initially, the mice are clumsy and inefficient. The second piece of footage is of an experimental mouse who learned the task within 7 days. The key strategy is that the mouse brings its hind paw to the same rung as its forepaw to advance the wheel. (MacKenzie et al., Science/AAAS 2014)].
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