Old Memories Can Prime Brains to Make New Ones

Creating a memory takes energy, and brains only have so much. A study using snails shows how they can be primed for future learning.

Memories are shadows of the past but also flashlights for the future.

Our recollections guide us through the world, tune our attention, and shape what we learn later in life. Human and animal studies have shown that memories can alter our perceptions of future events and the attention we give them. “We know that past experience changes stuff,” said Loren Frank, a neuroscientist at the University of California, San Francisco. “How exactly that happens isn’t always clear.”

A new study published in the journal Science Advances now offers part of the answer. Working with snails, researchers examined how established memories made the animals more likely to form new long-term memories of related future events that they might otherwise have ignored. The simple mechanism that they discovered did this by altering a snail’s perception of those events.

The researchers took the phenomenon of how past learning influences future learning “down to a single cell,” said David Glanzman, a cell biologist at the University of California, Los Angeles who was not involved in the study. He called it an attractive example “of using a simple organism to try to get understanding of behavioral phenomena that are fairly complex.”

Although snails are fairly simple creatures, the new insight brings scientists a step closer to understanding the neural basis of long-term memory in higher-order animals like humans.

Though we often aren’t aware of the challenge, long-term memory formation is “an incredibly energetic process,” said Michael Crossley, a senior research fellow at the University of Sussex and the lead author of the new study. Such memories depend on our forging more durable synaptic connections between neurons, and brain cells need to recruit a lot of molecules to do that. To conserve resources, a brain must therefore be able to distinguish when it’s worth the cost to form a memory and when it’s not. That’s true whether it’s the brain of a human or the brain of a “little snail on a tight energetic budget,” he said.

On a recent video call, Crossley held out one such snail, a thumb-size Lymnaea mollusk with a brain he called “beautiful.” While a human brain has 86 billion neurons, the snail’s has only 20,000—but each of its neurons is 10 times larger than ours and much more accessible for study. Those giant neurons and their well-mapped brain circuitry have made the snails a favorite subject for neurobiology research.

Researchers at the University of Sussex traced a learned behavior in Lymnaea snails to a circuit of just four neurons in its brain.

Photograph: Michael Crossley; Kevin Staras/Quanta Magazine

The tiny foragers are also “remarkable learners” that can remember something after a single exposure to it, Crossley said. In the new study, the researchers peered deep into the snails’ brains to figure out what happened at the neurological level when they were acquiring memories.

Coaxing Memories

In their experiments, the researchers gave the snails two forms of training: strong and weak. During strong training, they first sprayed the snails with banana-flavored water, which the snails treated as neutral in its appeal: They would swallow some but then spit some of it out. Then the team gave the snails sugar, which they gobbled up avidly.

When they tested the snails as much as a day later, the snails showed that they had learned to associate the banana flavor with the sugar from that single experience. The snails seemed to perceive the flavor as more desirable: They were much more willing to swallow the water.

In contrast, the snails did not learn this positive association from a weak training session, in which a bath flavored with coconut was followed by a much more diluted sugar treat. The snails continued to both swallow and spit out the water.

So far, the experiment was essentially a snail version of Pavlov’s famous conditioning experiments in which dogs learned to drool when they heard the sound of a bell. But then the scientists looked at what happened when they gave the snails a strong training with banana flavoring followed hours later by a weak training with coconut flavoring. Suddenly the snails learned from the weak training, too.

When the researchers switched the order and did the weak training first, it again failed to impart a memory. The snails still formed a memory of the strong training, but that didn’t have a retroactive strengthening effect on the earlier experience. Swapping the flavors used in the strong and weak trainings also had no effect.

The scientists concluded that the strong training pushed the snails into a “learning-rich” period in which the threshold for memory formation was lower, enabling them to learn things they otherwise would not have (such as the weak-training association between a flavor and dilute sugar). Such a mechanism could help the brain direct resources toward learning at opportune times. Food could make the snails more alert to potential food sources nearby; brushes with danger could sharpen their sensitivity to threats.

A Lymnaea snail that associates flavored water with sugar rapidly opens and closes its mouth to swallow it (right).

A snail that has not learned that association keeps its mouth closed (left).Video: Michael Crossley, Kevin Staras/Quanta Magazine

However, the effect on the snails was fleeting. The learning-rich period persisted for only 30 minutes to four hours after the strong training. After that, the snails stopped forming long-term memories during the weak training session, and it wasn’t because they had forgotten their strong training—the memory of that persisted for months.

Having a critical window for enhanced learning makes sense because if the process didn’t turn off, “that could be detrimental to the animal,” Crossley said. Not only might the animal then invest too many resources into learning, but it could learn associations harmful to its survival.

Altered Perceptions

By probing with electrodes, the researchers found out what happens inside a snail’s brain when it forms long-term memories from the trainings. Two parallel tweaks in brain activity occur. The first encodes the memory itself. The second is “purely involved in altering the animal’s perception of other events,” Crossley said. It “changes the way that it views the world based on its past experiences.”

They also found that they could induce the same shift in the snails’ perception by blocking the effects of dopamine, the brain chemical produced by the neuron that activated the spitting behavior. In effect, that turned the neuron for spitting off and left the neuron for swallowing constantly on. The experience had the same carryover effect that strong training did in the prior experiments: Hours later, the snails formed a long-term memory of the weak training.

The researchers thoroughly and elegantly map out the process from “the behavior to the electrophysiological underpinnings of this interaction between past and new memories,” said Pedro Jacob, a postdoctoral fellow at the University of Oxford who was not involved in the study. “Having the knowledge of how mechanistically this happens is interesting because it’s probably conserved across species.”

Frank, however, isn’t fully convinced that the failure of the snails to ingest flavored water after the weak training means they carried no memory from it. You can have a memory but not act on it, he said, so making that distinction may require follow-up experiments.

The mechanisms behind learning and memory are surprisingly similar in mollusks and mammals such as humans, Glanzman said. As far as the authors know, this exact mechanism hasn’t been shown in humans, Crossley said. “It may be a broadly conserved feature and therefore one which deserves further attention,” he said.

It would be interesting to study whether a shift in perception could be made more permanent, Glanzman said. He suspects that this might be possible if the snails are given an aversive stimulus, something that makes them sick instead of something they like.

For now, Crossley and his team are curious about what happens in the brains of these snails when they perform multiple behaviors, not just opening or closing their mouths. “These are quite fascinating creatures,” Crossley said. “You don’t really expect these animals to be able to do these kinds of complex processes.”

Source

(May require free registration to view)