It takes a lot of connections to create human intelligence. Brain function depends on contacts between multiple regions within the brain. To study how this connectivity is possible—and how it can go awry—international researchers led by the University of Tokyo have grown a working model of a cerebral tract in the lab. The study was published today in iScience.
The researchers grew spheroids of neurons that mimicked the cerebral cortex using human induced pluripotent stem cells (iPSCs). When two spheroids were placed at two ends of a microdevice that provided physical instructions, they extended axons toward each other along the narrow channel that separated them.
“After 25 days, both tendrils of axons reached all the way down the channel, and the two cortical spheroids were connected,” says senior author Yoshiho Ikeuchi. “We know this was a functional electrical connection, because if one spheroid was electrically stimulated, the other would respond after a short delay. This resembles the situation in a real brain, where distant regions communicate during cognition.”
These “cerebral tracts” only grew in the right circumstances. When one end of the microdevice was empty, axons still emerged from the neurons at the other end—but significantly less efficiently. Placing an object such as a glass bead at the empty end did nothing to improve fascicle growth.
“The spheroids promoting each other to grow fascicles is very interesting,” says first author Takaaki Kirihara. “It implies that opposing axons mutually guide each other, connecting two groups of neurons. This could help explain how reciprocal connections are formed between distant regions of the brain, sometimes even between different hemispheres.”
Although axons in a microdevice are by no means the same as a living brain, there is a clue that the tissue culture model was realistic. The gene L1CAM is known to be essential for cerebral tract formation. When L1CAM was knocked-down in the spheroids, many of the axons failed to assemble into a bundle. This suggests that the model could be used to study not only normal brain tissue but also developmental disorders of the cerebral tract.