The mechanisms of tadpole brains could provide scientists with new information on how autism develops in humans.
Researchers from The Scripps Research Institute have found that a key to neuroplasticity in tadpoles is not just the presence of new proteins, but how the brain makes proteins in the first place, pointing to a possible new role for proteins in sensory processing for people with autism spectrum disorder.
“The idea that visual experience can influence how we make proteins is something brand new,” Hollis Cline, PhD, Hahn Professor of Neuroscience and co-chair of the Department of Neuroscience, said in a statement. “This is interesting to think about because we live in a very busy sensory world.”
The team focused on tadpoles that have naturally translucent skin, making them a good model for examining the wirings of a living brain.
The tadpoles the researchers used were kept in the dark and exposed to either ambient light for the control group or a screen with moving bars for four hours to simulate normal visual experiences.
The researchers measured changes in protein expression—the production of protein in cells—before and after each experiment, and found that the expression of 83 proteins either shifted up or down in the experimental group.
While many of the proteins were considered effector proteins or proteins doing specific jobs in cells, the researchers also found three outliers—eIF3A, FUS and RPS17—that are regulatory proteins. The three regulatory proteins construct the machinery that makes the effector proteins further down the line, which contradicts the prevailing thought that regulatory protein expression holds steady even when visual experience varied.
Further analysis showed that the regulatory proteins are essential for learning from visual experience, where cells are better at building connections and reinforcing learning when they synthesize the proteins at a certain rate during visual experience.
The researchers found they could tag neurons with fluorescent proteins to see the physical signature that visual experience left in the brain. Because of eIF3A, FUS and RPS17, tadpoles had significant neuronal growth—seen in how their neurons sent out branch-like tendrils—after just four hours of visual experience.
The team then looked at whether changes in protein expression affected tadpole behavior by having the animals swim above a screen that project large, predator-like spots and tracked whether the tadpole would turn to avoid the dark spots.
The tadpoles with exposure to visual experience did significantly better on the avoidance test than tadpoles in the control group, suggesting that they had formed the neural circuits to better process visual information.
Tadpoles did not do as well on the test—even after exposure to visual experience—when they could not express all three key proteins, confirming the importance of the regulatory proteins in neuronal plasticity.
Finally, the team cross referenced their list with two databases—one of people with risk factors for autism spectrum disorders, and one with people with fragile X syndrome, which has similar characteristics as autism—to see whether the 83 total proteins were expressed differently in human brain disorders.
Here they found that 25 percent of the proteins on the list overlapped with the database lists of genes thought to cause autism spectrum disorder and fragile X syndrome.
Cline thinks mutations in regulatory proteins might keep some people from expressing the other proteins needed for processing sights, smells, textures, tastes and sounds.
The study was published in eLife.