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Study may reverse century-old understanding of the shape of ‘arms’ on mammals’ brain cells

Could Everything We Know About Brain Cell Connections Be Wrong?

Scientists at Johns Hopkins Medicine have made a groundbreaking discovery that could fundamentally change our understanding of how the brain works. For over a century, textbooks have depicted the long, slender arms of brain cells, called axons, as smooth cylinders. However, new research suggests these connections might actually look more like strings of pearls.

"Understanding the structure of axons is crucial because they act as the communication cables of our brain, enabling learning, memory, and other essential functions," explains Dr. Shigeki Watanabe, Associate Professor of Cell Biology and Neuroscience at Johns Hopkins University School of Medicine.

The discovery was unexpected. Researchers initially noticed these pearl-like structures, called non-synaptic varicosities, while studying the nervous systems of worms. Intrigued, they delved further, collaborating with colleagues at the University of California San Diego School of Medicine and employing advanced imaging techniques.

Using high-pressure freezing electron microscopy, a technique that preserves tiny structures by flash-freezing them, the team was able to capture detailed images of mouse neurons. They observed these "pearled" structures across various types of neurons, suggesting it is a common feature, not an anomaly.

“These findings challenge a century of understanding about axon structure,” says Dr. Watanabe.

But why the pearls? Through mathematical modeling and experiments, the scientists discovered that the shape and size of these pearls are influenced by factors like sugar concentration and the composition of the axon membrane.

They found that increasing sugar levels or decreasing tension in the membrane led to smaller pearls. Removing cholesterol from the membrane, which altered its stiffness, resulted in less vibrant pearls and reduced electrical signaling speed.

Further experiments revealed that applying high-frequency electrical stimulation caused the pearls to swell even larger and increased signal transmission speed.

The team plans to investigate whether these "pearled" axon structures also exist in human brains, both those of healthy individuals and those affected by neurodegenerative diseases. Their findings could offer valuable insights into brain function and how diseases like Parkinson’s might disrupt these delicate connections.

"These findings are only the beginning," says Dr. Watanabe. "They open up many exciting new avenues for research into the complex world of brain circuitry."

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