Scientists have known for more than a century that a single-celled organism with no nerve cells — much less a brain — can behave in ways that resemble learning. But those observations only went so far. How the organism did that was a mystery.
Now, scientists at UC San Francisco can explain how this simple organism, called Stentor coeruleus, learns: It uses molecular machinery that resembles what neurons have in the human brain. The results suggest that learning may be a fundamental feature of life.
In findings published in Current Biology , the researchers used modern neuroscience tools to study the pond-dwelling Stentor, which is shaped like a trumpet and is large enough to be seen with the naked eye. These organisms contract when perturbed but stop after repeated jolts — a form of learning called habituation.
"We usually think learning must arise from large networks of neurons," said Wallace Marshall , PhD, professor of Biochemistry and Biophysics at UCSF and senior author of the paper, which appeared on April 22. "But these single cells can perform behaviors that normally are associated with cognition and brains."
To understand how the Stentor learns, UCSF researchers built a device that jostled them in petri dishes once a minute. Over time, the Stentors became insensitive to the jolts and stop retracting their tails.
The researchers then treated the Stentors with drugs that disrupted their ability to produce new proteins, assuming that like animal neurons, they would no longer be able to learn. Instead, the Stentors learned to ignore the disturbances even more quickly. It turned out Stentors rely on a different mechanism to store memories: modifying the proteins they already have.
"We've long thought that forming a memory meant making a molecule, and forgetting meant losing it," Marshall said. "Here, it seems to work in a different way."
The scientists also measured gene expression and protein levels and used drugs to track what was happening as the Stentors adapted.
The results suggest that Stentors reacted to the jolts by allowing calcium to flow into their cells, which triggered an enzyme called CaMKII to add chemical tags to certain proteins. With each jolt, the Stentors became less likely to respond — suggesting the chemical tags had changed how the organisms sensed the jolts. The Stentors also passed this knowledge to their daughter cells when they divided.
Scientists are still trying to understand how Stentors store this knowledge, but it may involve mechanoreceptors, which respond to touch. Animal neurons do something similar using CaMKII to change the sensitivity of receptors on their surface. It's a tantalizing clue that learning may rely on molecular systems that existed long before the evolution of brains.
"Stentors and humans might not seem alike at all," Marshall said. "But learning in both involves protein changes and calcium signaling, and it's possible our brain cells may have borrowed this mechanism from earlier cells that could learn on their own."
Authors: Other UCSF authors are Deepa H. Rajan; Ashley Albright, PhD; Ulises Diaz, PhD; and Yina Hudnall.
Funding: This work was supported by the National Institutes of Health (R35 GM130327); European Molecular Biology Laboratory; European Commission; EMBO; National Science Foundation; and Fondation Fourmentin-Guilbert.
