Recent research led by Shigeki Watanabe at Johns Hopkins University and Graham Knott at the Swiss Federal Technology Institute of Lausanne has revealed that axons, previously thought to be smooth and cylindrical, actually exhibit a pearls-on-a-string morphology.

Watanabe first observed this unique axon structure in healthy Caenorhabditis elegans neurons during his graduate studies, later collaborating with Knott, who noted similar patterns in mouse brain slices.

The research team investigated the relationship between axon shape and function, particularly focusing on the placement of sodium channels and how it affects action potential firing.

Simulations demonstrated that pearled axons, with sodium channels spaced at approximately 190 nanometers, fired action potentials faster than their cylindrical counterparts, highlighting the importance of axon structure in neuronal signaling.

This study emphasizes that the physical properties of the brain can provide valuable insights into the regulation of signal propagation within neurons.

Watanabe's hypothesis suggests that the physical properties of the axon membrane, especially tension, play a crucial role in the formation of these pearls.

Experiments manipulating osmotic pressure revealed that higher osmotic pressure reduced the size and spacing of the pearls, while lower osmolarity had the opposite effect, indicating a dynamic relationship.

Further experiments showed that removing cholesterol from neuron membranes decreased their rigidity, altering axon shape and reducing pearling, thus reinforcing the connection between membrane properties and axon morphology.

Using electron microscopy, the researchers analyzed unmyelinated axons in mice, finding pearls spaced about 200 nanometers apart along axons with a diameter of 60 nanometers.

To preserve axon morphology for their studies, the team employed high-pressure freezing techniques, which prevented the shrinkage typically caused by traditional fixation methods.

Their findings, published in Nature Neuroscience, suggest that pearling is a common feature in all unmyelinated axons and may not necessarily indicate neurodegenerative conditions.

Looking ahead, future research will investigate the presence of pearling in human neurons and how axon morphology may change during sleep, potentially affecting fluid dynamics and waste clearance.