Scientists at the University of California - Berkeley are revolutionising the way we look at the growth and development of neurons as they form connections with each other to allow our brains to process information. They’ve developed the next best thing to cracking open a skull and peering inside at the brain: A three-dimensional, artificial neural network, constructed with tiny beads.
Ehud Isacoff, a biophysicist with a dual appointment at Berkeley Lab’s Physical Biosciences and Materials Science division and UC Berkeley’s Department of Molecular and Cell Biology, developed the idea (along with Sophie Pautot and Claire Wyart, both of the Department of Molecular and Cell Biology), because he believes the more realistic the method of studying neural networks, the better our understanding of the brain. “The brain is a multilayered structure, with billions of neurons interconnected in complicated ways,” he reminds us. “Some neurons have 100,000 connections.”
The scientists grew neurons on beads measuring several dozen microns in diameter. These beads assemble themselves into hexagonal sheets, which can be layered on top of each other - a bit like a stack of pancakes - to produce a three-dimensional scaffolding. This scaffolding allows the observation of neuronal growth just as it would occur in the brain: Scientists can watch neurons grow, connect, and communicate with other neurons in all directions. This technique is a dramatic improvement over current lab-based methods of studying neural networks, in which neurons are grown on two dimensional plates - providing a very crude approximation of the actual network structure forming in our three-dimensional brains.
"Our 3D neural network will help us understand how connectivity emerges when neurons grow, and how these connections change over time," said Isacoff.
In fact, being able to create a 3D neural network at all is an exceptional feat. Previous attempts at growing a three-dimensional neural network have been wildly unsuccessful, mostly because neurons are very finicky - they’ll die if they’re ripped from their surface and stacked atop another neuron, or they’ll just settle back into the surface. Although the two-dimensional models have increased scientists’ understanding of how neurons reach out and connect with each other, Isacoff and his colleagues realised a better model was needed - simply because the brain is a three-dimensional structure. “We knew that neurons grow on a flat surface,” said Isacoff. “So we thought we could trick them and grow them on a spherical bead that appears flat to a neuron, just like Earth appears flat to us.”
The finicky neurons obliged, and grew on the tiny beads, which were then placed in solution to order themselves into a highly structured, two-dimensional array. These arrays of beads were then stacked on top of each other, forming the three-dimensional scaffolding that allows neurons to connect with each other in three dimensions. Fluorescence microscopy imaging of the structure revealed the development of a three-dimensional web of neurons, as densely packed as neural networks in the brain.
"Of course, the brain is much more complicated, but this is a start," said Isacoff.
If the complexity of the brain can be mirrored in an easy-to-develop system, we could gain fundamental insights into how neural networks enable phenomena of everyday life: Seeing, hearing, kicking a football, or reading this blog. Such a system could be used to gauge the effectiveness of drug therapies that target neurodegenerative diseases like Alzheimer’s and Parkinson’s. It could also help design computer processor architectures that mimic the brain’s ability to optimise neural networks as new skills are learned.
The full paper, entitled “Colloid-guided assembly of oriented 3D neural networks”, can be found here.
The image above shows a computer simulation of their results from their paper, originally published in Nature.