In the late 1800s, Spanish neuroscientist Santiago Ramón y Cajal drew hundreds of images of neurons. His exquisite work has influenced our understanding of the shape of cells. Cells with a bulb in the center, a forest of tree-like branches at one end, and a long, smooth tail at the other.
Centuries later, these images still remain in textbooks. But a controversial study suggests that Ramón y Cajal and subsequent neuroscientists may have missed an important detail.
A team at Johns Hopkins University discovered small “bubbles” called axons along their long tails. Axons, usually described as mostly smooth cylindrical cables, may instead look like “pearls on a string.”
Why do you care? Axons transmit electrical signals that connect the neural networks that generate our thoughts, memories, and emotions. Small changes in shape can change these signals and, potentially, the brain’s output, and therefore our behavior.
“Understanding the structure of axons is important for understanding brain cell signaling,” said Shigeki Watanabe of the Johns Hopkins University School of Medicine, who led the study, in a press release.
The study utilized a type of microscope that better preserves neuron structures. In three types of mouse neurons – some grown in Petri dishes and some grown in adult mice and mouse embryos – the team consistently identified nanopearls, suggesting that they are part of the normal morphology of axons.
“These findings challenge a century of understanding of axon structure,” Watanabe said.
Nanopearls were not static. Adding sugar to the neuron’s liquid environment or removing cholesterol from the neuron’s membrane (the fatty protective outer layer) changed the size and distribution of the nanopearls and caused their velocity signal to travel along the axon.
Reaction to the study was divided. Some scientists welcomed the discovery. Over the past 70 years, scientists have extensively studied axon shape and recognized its complex structure. With advances in microscopy technology, discovering new structures is not surprising, but rather exciting.
Others are more skeptical. speaking science“I think it’s true that (axons) are not perfect tubes, but what they show is also not just this kind of accordion,” said Christophe Leterrier of Aix-Marseille University, who was not involved in the study.
Cables prone to stress
Axons extend inches from the brain with a diameter 100 times thinner than a human hair. Although they are mostly tubular, they are occasionally dotted with bubbles called synaptic varicosities, which contain chemicals for the transmission of information to neighboring neurons. There are mainly two types of these long branches. Some are encased in a fat shell, while others are “bare” without any cushioning.
Although often compared to tree branches, axons are shapeshifters. For example, a brief burst of electrical signals temporarily enlarges synaptic varicosities by up to 20%. Additionally, axons may widen slightly for long periods of time and then return to their normal size.
These small changes have a big impact on brain calculations. Like an electrical cable that can change its properties, fine-tune the signal strength between the networks and, consequently, the overall functioning of the neurons.
Axons have another secret. An unexpected blow to the head during exercise or an injury such as Alzheimer’s or Parkinson’s disease can reduce you to a “stress ball.” Stress balls are relatively large compared to synaptic varicosities. But it’s temporary. The structure eventually loosens and regains its tubular shape. Rather than being harmful, it is more likely to protect the brain by limiting damage to a smaller area and foster axons during recovery.
However, the ability of axons to transform is temporary and often occurs only under duress. What do axons look like in a healthy brain?
pearls on a string
About 10 years ago, while developing new microscopy techniques, Watanabe noticed tiny bubbles in the axons of roundworms. The structures were much smaller and more tightly packed than stress balls, but he regarded the results as a curiosity and did not investigate further. A few years later, Pawel Burkhardt of the University of Bergen discovered pearly axons in the comb jelly, a small marine invertebrate.
In the new study, Watanabe and colleagues used a new microscopy technique, high-pressure freezing, to reexamine the head-scratching results. To image the brain’s fine details, scientists typically administer several chemicals to hold neurons in place. The processed brain is then sliced into very thin slices and the slices are individually scanned under a microscope.
The procedure takes several days. If you’re not careful, they can distort the membranes of neurons and damage or even shred delicate axons. In contrast, high-pressure freezing better fixes the morphology of cells.
Using electron microscopy, which beams electron beams at the cells to outline their structure, the team studied ‘primary’ axons from three sources: rat neurons grown in laboratory dishes and neurons from thin slices of adult and embryonic rat brains. .
All axons had distinctive pearl-like stains along their entire length. At roughly 200 nanometers in diameter, the nanopearls are much smaller than stress balls and are spaced closer together. Due to biophysics, beads are likely to form. Recent research has shown that when tension is applied, parts of the long tubes crumple into beads. This phenomenon is called “membrane-based instability.” Why this happens and how it affects brain function remains largely a mystery, but the team has an idea.
Is seeing believing?
They used mathematical simulations to model how changes in the surrounding environment affect the pearling and electrical transmission of axons.
Axons are surrounded by a sticky protective protein gel, like a bubble suit. However, they still experience the same physical force that we experience when we quickly click our heads. Simulations revealed that the physical tension surrounding neurons plays an important role in governing axonal pearl formation.
In another test, the team removed cholesterol from neurons, a component of their cell membranes, making them more flexible and fluid. This adjustment reduced furling in the simulation and slowed down the electrical signals passing through the simulated axon.
Recording electrical signals from living rat neurons gave similar results. Smaller, more densely packed nanopearls slowed down the signal, while larger, more widely spaced axons resulted in faster transmission.
The results suggest the “intriguing idea” that changes in biophysical forces can directly change the speed of electrical signaling in the brain, the authors wrote.
Not everyone is convinced.
Some scientists believe nanopearls are artifacts of the preparation process. “Flash freezing is a very fast process, but things can happen that cause beading while manipulating the sample,” said Pietro De Camilli of the Yale School of Medicine, who was not involved in the study. science. Others question whether nanopearls, like stress balls, form during stress and eventually unfold. We don’t know yet. A microscope is a snapshot in time rather than a movie.
Despite the backlash, the team is switching to human axons. Healthy human brain tissue is difficult to obtain. They plan to look for traces of nanopearls in brain tissue removed during epilepsy surgery and in brain tissue that has died from neurodegenerative diseases. Brain organoids, or “mini-brains,” developed in healthy people may also help decipher axon shapes.
Nonetheless, this study prompted the following questions: What else have we been missing when it comes to brain anatomy?
Image Credit: Life Sciences Image Library by Fayette Reynolds on Unsplash
