Learning where memories are born.

It happens when we sleep, says Scientific American. It happens in cells that aren’t even neurons:

A new study from the University of Toronto, published on-line this week in the journal Neuron furnishes support for this theory. It provides evidence that the basic act of learning whether one’s environs are safe or not, a behavior common to all animals, depends on glial cells that form the fatty sheath called myelin—electrical insulation that covers nerve fibers. The new theory postulates that establishing indelible memories that can be recalled long after sensory input or training on a task involves an interaction between glia and peculiar brain waves produced during sleep.

Traditionally researchers who study the myelin insulation on nerve fibers, called axons, have focused on diseases, such as multiple sclerosis, in which the fatty sheath is damaged. In multiple sclerosis, neural transmission fails, causing wide-ranging disabilities. Much like the plastic coating on a copper wire, myelin was understood to be vital for neural transmission but inert and irrelevant to information processing and memory storage.

The new research challenges that view because of the discovery that the glial cells that form myelin, called oligodendrocytes, can detect neural impulses flowing thorough the axons they contact. Intriguingly, immature oligodendrocytes, called oligodendrocyte progenitor cells (OPCs), populate nearly the entire brain with little regard for the complex anatomical boundaries within brain tissue. Salted throughout the brain—even in adulthood when there would seem to be little need for immature brain cells—OPCs are by far the most abundant cells undergoing cell division in our brain.

In the Neuron study, first author Patrick Steadman and colleagues in the laboratory of Paul Frankland at the Hospital for Sick Children and University of Toronto, tested the hypothesis that new myelin must form during learning. They did so by genetically altering mice so that a gene called myelin regulatory factor (MRF) is deleted when treated with the drug tamoxifen. The gene is essential for OPCs to mature into oligodendrocytes. Knocking out MRF increased the number of OPCs, whereas the number of newly formed oligodendrocytes diminished.

Now the researchers could test the hypothesis that formation of myelin is necessary for learning by training these mice while preventing them from forming new myelin. They could block myelin formation at any point during training or afterward simply by administering tamoxifen to the mice.

They then probed whether myelin is needed for learning by giving a well-established memory test called the Morris water maze, in which a mouse is placed in a large tub of water in which a hidden platform is submerged just below the surface. The mice quickly learned where that platform was, and they swam directly to it after several days of training. The experiments showed that the mice that were unable to form new myelin were able to learn where the platform was just as quickly as control mice, but when their recall was tested long after training ended, the ones that could not form new myelin did not remember the location as well and had to swim for a longer time to find the platform again. Examining the brain tissue with an electron microscope, the researchers found that more axons were myelinated in regions of the brains of normal mice known to be required for learning the Morris water maze. The researchers now had evidence that myelin is involved in making the long-term memories involved in learning.

[T]hey trained the mice, as before, three times a day for six days and then administered tamoxifen after the training had ended to inhibit myelin formation. When tested 28 days later, the mice that could not form new myelin after the training session performed poorly in recalling where the hidden platform was. If they waited too long after training to inhibit the formation of new myelin—25 days in their tests—recall was not impaired, indicating that a window of time persists after training when new experiences become consolidated into memory. The results suggest that new myelin is part of the process of engraving lasting memories.