One of the most familiar drawings in biology textbooks may need an update. Scientists studying the microscopic structure of brain cells have found evidence that some axons do not look like the smooth tubes students have seen for generations.
Instead, certain unmyelinated axons in the mammalian central nervous system appear more like strings of tiny pearls. The discovery challenges a basic picture of neuron anatomy that has lasted for more than a century.
The research comes from scientists at Johns Hopkins Medicine and their collaborators. Their peer-reviewed study, published in Nature Neuroscience, used advanced imaging methods to examine axons while trying to preserve their natural shape.
The result was surprisingly consistent. Across tens of thousands of images of mouse neurons, researchers found repeating nanoscale swellings along axons. They call these structures “nonsynaptic varicosities.”
Brain Axons May Look More Like Strings of Pearls
Scientists already knew that axons can contain larger bulges called synaptic varicosities. These structures are associated with communication between nerve cells and can contain neurotransmitter-filled vesicles.
However, the Johns Hopkins team found something different. The axons they examined contained much smaller swellings that appeared repeatedly along their length, rather than only at communication sites. Researchers measured these nanoscale pearls at about 200 nanometers across. Thin connecting sections between them measured roughly 60 nanometers in diameter, producing a pattern that resembles beads threaded onto a narrow string.
The team observed this shape in neurons grown in the laboratory, as well as neurons taken from adult and embryonic mice. The axons examined were unmyelinated, meaning they lacked the fatty myelin coating found around many other axons.
“Understanding the structure of axons is important for understanding brain cell signaling,” Johns Hopkins neuroscientist Shigeki Watanabe said when the findings were announced. He described axons as cables connecting brain tissue and supporting functions such as memory and learning.
Scientists have long known that pronounced axon beading can occur when neurons are injured or dying, including in some neurodegenerative conditions.
Why Scientists May Have Missed the Shape for So Long?
The century-old mistake may have less to do with careless observation and more to do with how scientists prepared samples. Looking at structures only a few hundred nanometers wide is not easy. Traditional electron microscopy often requires researchers to chemically fix and dehydrate biological tissue. Those steps make extremely small structures easier to examine, but they can also alter delicate cell membranes.
Watanabe offered a simple comparison. Preserving a structure through freezing can be thought of like freezing a grape, while dehydration is more like turning that grape into a raisin. The Johns Hopkins team used high-pressure freezing electron microscopy. Rapid freezing helped preserve the neurons closer to their natural physical state before scientists examined them at extremely high resolution.
The pearl pattern appeared again and again. Researchers reported seeing the nanoscale structures across tens of thousands of images, giving them reason to think the finding was not an occasional defect or imaging accident.
Tiny Pearls Could Affect How Brain Signals Travel
Researchers electrically stimulated neurons and watched the nanoscale structures change. The pearls became about 8% longer and 17% wider on average, with those physical changes lasting for at least 30 minutes.
The original Nature Neuroscience paper found that neuronal activity could alter membrane cholesterol, change the nanopearls, and slow action potential conduction. That finding suggests the physical geometry of an axon may help fine-tune how quickly electrical information moves.
Membrane physics appears to play a major role. Researchers worked with Padmini Rangamani and colleagues at the University of California San Diego to build mathematical models explaining how mechanical forces could create the pearl-like pattern.