Summary: New research reveals that even a small loss of myelin (the protective layer surrounding neurons) can severely alter the way the brain sends and interprets sensory information. By studying corticothalamic circuits in mice, scientists discovered that when the first segment of myelin closest to the neuron’s cell body degraded, nerve signals slowed down and lost their crucial “first wave,” altering the way sensory information was encoded.
This missing piece of signal changed the way the cortex and thalamus communicated, leaving the brain unable to correctly identify when or what the whiskers were touching. The findings shed light on why gray matter lesions in disorders such as multiple sclerosis cause disorientation, memory lapses, and difficulty navigating everyday environments.
Key facts:
Critical myelin loss: Damage near the neuron’s cell body disrupted the first “code segment” needed for accurate signal transmission. Broken communication loops: Corticothalamic circuits were still sending signals but with reduced precision, affecting sensory perception. Gray Matter Insight: The work explains why gray matter lesions produce severe cognitive symptoms in conditions such as MS.
Source: KNOW
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 disappears in cells that transfer signals over longer distances?
Maarten Kole’s research group studied this question in mice, looking specifically at the nerve fibers that travel from the outer layer of the brain to the thalamus, a crucial switching station deep in the center of the brain.
The processing of sensory information involves continuous communication between the outer layer of the brain (cerebral cortex) and the thalamus. Such an exchange occurs, for example, when mice explore their environment with their whiskers. This interaction is known as the corticothalamic loop.
These loops also help humans process sensory information and perform all kinds of cognitive tasks. In multiple sclerosis (MS), damage to myelin can lead to cognitive impairments, such as not being able to remember familiar names.
The most important nerve cells for exchanging information in these loops are those located in the fifth layer of the cerebral cortex of the brain.
“We actually know these cells very well, but we didn’t know what role myelin played in the process of transferring information to the thalamus,” explains Maarten Kole, group leader at the Netherlands Institute of Neuroscience.
Directed degradation of myelin
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, degradation only occurred in the parts located closest to the cell body.
This means that this method mainly mimics how MS develops in the areas where the cell bodies are located: the so-called gray matter lesions. With such injuries, cognitive problems are usually more severe and the prognosis worse.
In these cases, people with MS can no longer orient themselves correctly, notice problems when driving and have difficulty remembering the names of people they are familiar with.
Missing code snippet
The researchers found that the missing piece of myelin caused slower and less consistent signal transmission to the thalamus.
“We had anticipated this, because myelin is known to be essential for rapid signal transmission,” Kole explains, “but what was new for us was that we completely missed the first wave of signals.”
“You could compare it to a supermarket barcode: the scanner only recognizes a product if the entire barcode is scanned. But if you miss the first piece of myelin, you basically skip the first black stripe of the barcode. Because of this, the correct product can no longer be scanned.”
Unrecognizable environment
But what exactly is the impact of this missing piece of code? When a mouse’s whiskers touch an object, cells in the brain’s cerebral cortex act as an amplifier for the thalamus. This amplification helps the mouse more accurately determine what and where it is touching something.
“We saw that this amplification still occurs, but with less precision. Because of this, the communication circuit between these two areas of the brain is interrupted and the brain loses track. The mouse can still sense something with its whiskers, but it cannot identify exactly when or what,” explains Kole.
What does this mean?
Knowing the anatomy and function of these specific nerve cells is important for future research.
“We have known for a long time that these cells are wrapped in myelin in a very particular way,” Kole confesses.
“It’s one of the few cell types in which the first part in particular is so specifically isolated. Now we finally understand why that is.”
This knowledge forms the basis for our understanding of the symptoms that develop with gray matter lesions. We know that the brain continually generates codes. When the myelin in these nerve cells is lost, the codes change and communication in the brain is interrupted. This results in cognitive problems, such as having difficulty finding your way.
In the future, Kole’s team wants to investigate how the myelin damage in this area could be recovered. In this way, the severe symptoms associated with gray matter damage in MS may one day be alleviated.
Key questions answered:
A: This segment carries the first “strip” of the brain’s information code. Without it, the thalamus receives incomplete signals and cannot interpret the inputs correctly.
A: Signals arrive more slowly and less reliably, so the brain knows something happened but can’t determine “what” or “when,” leading to sensory confusion.
A: Gray matter lesions often remove myelin in this precise location, which explains why patients have difficulty with orientation, recognition, and other higher-order cognitive tasks.
Editorial notes:
This article was edited by a Neuroscience News editor. Magazine article reviewed in its entirety. Additional context added by our staff.
About this news in sensory neuroscience and myelin research
Author: NIN Communication
Source: KNOW
Contact: NIN Communication – KNAW
Image: Image is credited to Neuroscience News.
Original research: Open access.
“Corticothalamic coincidence detection of layer 5 myelination gates” by Maarten Kole et al. Nature Communications
Abstract
Corticothalamic coincidence detection of layer 5 myelination gates
Myelin is essential for the rapid conduction of action potentials (APs), but its role in the long-term processing of disparate inputs remains unclear.
Here, using a cell type-specific approach, we recorded optogenetically evoked pyramidal neuron responses via in vivo juxtacellular patch probes and Neuropixels, tracking spike transmission from layer 5 (L5) to the posteromedial thalamic nucleus (POm) in the mouse.
Cuprizone-induced demyelination caused millisecond-scale delays, increased temporal restlessness, and impaired transmission of high-frequency AP bursts. Computational modeling of saltatory propagation from L5 to POm revealed that loss of myelin from neocortical internodes acts as a low-pass filter, preventing high-frequency spikes within the burst.
Finally, combining optogenetic stimulation with whisker input showed that intact myelination is crucial for coincidence detection in the thalamus.
These findings suggest that the continuous myelin pattern of L5 axons not only accelerates conduction but also allows precise temporal integration of sensory and cortical signals through long-range pathways.
