A new mouse model study suggests that the degradation of myelin closest to the cell body of neurons may be key to slower and less consistent signal transmissions. The findings could eventually lead to recovering from myelin damage.

Our nerve cells are surrounded by a protective layer (myelin). This protective layer allows signals to pass between cells incredibly quickly. But what happens when this layer goes missing from cells that transfer signals over longer distances? A Netherlands Institute for Neuroscience research group studied this question in mice, looking specifically at nerve fibers travelling from the brain’s outer layer to the thalamus, a crucial switching station deep in the middle of the brain. 

Processing sensory information involves continuous communication between the brain’s outer layer (cerebral cortex) and the thalamus. Such an exchange, for example, occurs when mice explore their environment with their whiskers. This interaction is known as a corticothalamic loop.

These loops also help humans process sensory information and perform all sorts of cognitive tasks. In multiple sclerosis, damage to myelin can result in cognitive impairments, like not being able to recall familiar names.

The nerve cells that are most important for information exchange in these loops are those located in the fifth layer of the brain’s cerebral cortex. To explore this role, the researchers administered a toxic substance that breaks down myelin. They expected this would cause the entire nerve fiber to lose its myelin. But instead, the degradation only occurred in the parts located closest to the cell body.

This means this method mostly imitates how MS develops in areas where the cell bodies are located: the so-called grey matter lesions. With such lesions, the cognitive problems are often more severe and the prognosis worse. In these instances, people with MS can’t orient themselves properly anymore, notice problems when driving, and struggle to recall the names of people familiar to them.

The researchers discovered that the missing piece of myelin resulted in slower and less consistent signal transmission to the thalamus. Researchers compare it to a barcode in the supermarket: the scanner only recognizes a product if you scan the entire barcode. If the first piece of myelin is missed, then the first black stripe of the barcode is skipped. Because of this, the right product can’t be scanned anymore.

But what is the exact effect of this missing piece of code? When the whiskers of a mouse touch an object, the cells in the brain’s cerebral cortex act as an amplifier of the thalamus. This amplification helps the mouse more accurately determine what and where it’s touching something.

The researchers found this amplification was still happening, but less accurately. Because of that, the communication loop between these two brain areas is disrupted, and the brain loses track. The mouse can still feel something with its whiskers, but it can’t exactly identify when or what.

Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, insight into the anatomy and workings of these specific nerve cells is important for future research.

This knowledge forms a basis for understanding of symptoms that develop with grey matter lesions. The brain is continuously generating codes. When myelin on these nerve cells is lost, the codes change, and that communication in the brain is disrupted. This results in cognitive problems, like struggling to orient oneself.

In the future, the research team wants to investigate how myelin damage in this area could be recovered. That way, the severe symptoms linked to the grey matter lesion in MS can one day be alleviated.

The findings were published in the journal Nature Communications.