Nerve insulation renewed to create long-term learning

A new study published in February 2020, in the journal Nature Neuroscience, shows that short-term learning occurs rapidly, but for it to become a long-term memory, brain cells must form more myelin, an insulating fatty material.

Memories are tricky. While some last lifelong, others fade quickly. The mechanism behind memory creation is still unknown, but details are coming to light bit by bit, some quite surprising. One is the discovery that myelin underlies the creation of long-term learning.

If this is pursued, it could allow new therapies to be developed to treat distressing conditions caused by unwanted and intrusive memories, such as post-traumatic stress disorder (PTSD). The reason for such persistent memories is the strong imprint created by these neurological events on the brain tissue.

The current study found that, in mice, a threatening situation induced a fearful response, which quickly became learned. However, this was associated simultaneously with more far-reaching brain changes. We find that a single, brief fear-learning experience can cause long-term changes in myelination and associated neurophysiological changes within the brain that can be detected even a month later.”

Myelin

Myelin is a white smooth fatty substance that lines many of the nerve fibers (axons) in the body. Myelin is formed by specialized brain cells called oligodendrocytes, that enwrap the nerve fibers originating from certain nerve cells. This repeated wrapping forms a thick covering composed of protein as well as fat.

Oligodendrocyte forms insulating myelin sheaths around neuron axons in the central nervous system. Image Credit: Juan Gaertner / Shutterstock
Oligodendrocyte forms insulating myelin sheaths around neuron axons in the central nervous system. Image Credit: Juan Gaertner / Shutterstock

It is known to be an insulator but forms an interrupted sheath over the fiber. The bare spots are called the nodes of Ranvier and allow nerve impulses to travel in a series of jumps from node to node, rather than continuously along the length of the fiber. This increases the speed of impulse travel.

This function is crucial to the best-used information networks in the brain, where a major part of the brain’s impulses travel to and fro. In these areas, some high-speed axons stretch 3 feet or more, despite being many times thinner than a single strand of hair. These long pathways give the brain the ability to respond instantly to the slightest command to move one or other muscle group to perform an action.

In the progressive muscular condition called multiple sclerosis, the hallmark is myelin damage and loss of muscle control. However, the changes undergone by myelin in the healthy brain are little understood.

One important discovery has been that myelin is formed within the brain when long-term memories are formed, and especially when the individual is learning a complex muscular movement such as roller-skating, as well as when a space-associated learning is taking place (if a mouse in a maze is learning the way back to its earlier location. This finding has been a crucial addition to the already known fact that new neuronal connections are made when long-term learning is taking place.

The study

The experimenters used mice, kept in a conditioning chamber with a range of environmental cues while a small electrical shock was given to the foot of each mouse. The researchers found that the mice rapidly learned to fear the specific environment associated with the previous shock. After just one exposure the mouse froze when it was put back in that environment, even when no shock was given. The scientists think this is an expression of the fear they remember in association with that environment.

These mice were now replaced with others who had been genetically modified so that they could not produce myelin. These mice also learned to fear the specific environment with one learning experience based on fear. They froze when exposed to that cue in the chamber even when no shock was experienced. However, their memories faded away quickly. In other words, without myelin formation, fear-based memories don’t consolidate and become permanent. These mice were also found to have long-lasting alterations to neural activity in the prefrontal cortex.

The present study adds to the existing evidence that myelin formation is essential to strengthening and maintaining these new connections so that the memory becomes persistent. In other words, myelin not only helps form and execute physical movements but in the establishment of durable memories.

How does myelin act to do this? It may be that its ability to enhance signal speed and efficiency of conduction along the axons helps to change the way important nerve signals travel along the major nerve networks.

Researcher Simon Pan comments, “This study is a significant advance in our understanding of how the brain remodels itself in response to a learning experience. A cardinal property of myelin is its stability, which uniquely positions it to support enduring, even life-long, memories in humans, mice, and other animals.”

Implications

Finding the exact role played by this substance in learning will help uncover the way learning is carried out, how memories are formed, and how mood and anxiety disorders can be treated and identified using these discoveries.

For instance, an earlier study found that, capitalizing on earlier research by Jonah Chan who is also involved in the current study, the antihistamine drug clemastine fumarate which could be useful in the treatment of multiple sclerosis could be used to establish even more lasting conditioned fear-induced memory in mice.

When veterans with PTSD underwent MRI of their brains, the hippocampal region of the brain seemed to have a higher than average myelin content. This is interesting because memory consolidation to transform them from short- to long-term memory occurs in this area.

The question is, could myelination be part of the reason, at least, for the abnormal function of memory in PTSD? Says Mazen Kheirbek, “Myelin plasticity could be beneficial for skilled learning such as playing a piano or remembering locations, but also detrimental if it leads to persistent, overgeneralized fear responses to everyday situations.”

Chan sums up, “We are now seeing that the process of oligodendrocyte generation and myelination can be quite dynamic in the normal adult brain. It's a form of plasticity that responds to experience and that causes long-lasting changes. This is a very recent concept that we are in the early days of exploring.”

Journal reference:

Pan, S., Mayoral, S.R., Choi, H.S. et al. Preservation of a remote fear memory requires new myelin formation. Nat Neurosci (2020). https://doi.org/10.1038/s41593-019-0582-1

Dr. Liji Thomas

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Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.

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