The researchers examine in the mind of the worm clues about the formation of memories.



A single adult worm crawling on the surface of a petri dish. Credit: Daniel Merritt

Try as you can, some events can not be recalled. Known in psychology as "blocking memory," the phenomenon has remained elusive since its first description more than half a century ago. Researchers at the Donnelly Center have now discovered that the blockage was not due to memory formation problems, as previously thought, but to memory recall – at least in the worms.

By studying this process in the C. elegans Worm, a creature of only a millimeter in length but whose biology has been so studied that the position of all its 302 nerve cells in the body is known, researchers believe to be able to identify the cells and molecules at play during the entire life cycle. learning and memory.

The results are described in a study published in the journal Scientific reports.

The blockage of memory, also called Kamin blockade, was first described in rats in the 1960s by psychologist Leon Kamin of McMaster University. This occurs when an animal that has already learned to respond to a signal, such as a sound, can not learn to respond to another signal, say a flash of light, when it is presented at the same time. time that the sound learned.

"Suppose you grew up hearing songs from ice cream singers playing a song and you heard that song, even when you do not see it, makes you think of ice cream," says Daniel Merritt, who led the study the group of Derek van der Kooy, professor at the Donnelly Cellular and Molecular Research Center and at the Department of Molecular Genetics of the University of Toronto. "One day, the owners of ice cream trucks decide to add a green light that turns on the roof of the truck, so even the hard of hearing can see them.Kamin Blocking predicts that you will not learn to associate green lights that turn with ice cream, because the song "ice cream truck" already fully predicts the delicious treat that is reserved for you. "

Blocking kamin is considered an essential means for human learning by focusing on novelty. This has led to a well-established idea that, to learn an experience, it must have an element of surprise. Blocking problems are pronounced in people with schizophrenia, which could decrease the selectivity of attention.

The process, however, has been difficult to study in detail in the mammalian brain because of its complexity and lack of molecular tools.

"Being able to fully describe the molecular changes that occur in memory is extremely appealing, but human memory is too fleeting and nebulous to pin it down," says Merritt. "But by studying this in worms, we are really moving forward to understand exactly what happens when memories are formed and recovered molecule by molecule."

The AWC neuron is required for learning about benzaldehyde memory. Future work will establish how it contributes to blocking memory. Credit: Daniel Merritt

It is thanks to a vast genetic and molecular toolbox available to researchers working with C. elegans. But first, Merritt had to establish that the blockage of memory occurred in worms, which had not been studied before.

To do this, it has led the worms to associate hunger with the taste of salt or the smell of benzaldehyde, which gives the almonds a sweet smell. Unlike unformed worms, which find both substances attractive, trained worms develop a strong aversion to them and crawl.

Then Merritt gave the worms formed to benzaldehyde benzaldehyde with salt. When he then exposed the worms to the salt alone, they crawled to her again. It was the same when salt-formed worms experimented with salt with benzaldehyde – they continued to like the smell of almonds. Whatever the signal received, it was blocked at the same time as the first one, as happens in rats and humans.

To deepen the operation of the blockage, Merritt repeated the experiment with worms expressing a protein called EGL-4 that was labeled with a green fluorescent molecule to make it visible.

The EGL-4 protein is present in a single olfactory nerve cell in the worm's head and its movement inside this cell is necessary for the learning of benzaldehyde deprivation. To Merritt's surprise, the protein changed position during benzaldehyde blockage in the same way as during normal learning. This suggests that the memory of not liking benzaldehyde was formed but could not be recovered – the worm forgot it.

"It's interesting because it goes against the classic interpretation of the blockage in which you need an element of surprise or do not remember the second association," says Merritt. "Our data shows that memory is formed but that is the expression of a behavior that has been removed in some way."

The effect of blocking lasts about four hours. What's going on in the worm's head during this time?

"That's the big question," says Merritt, who is currently working to uncover parts of the worm's brain that help integrate the learning responses of salt and benzaldehyde. "I'll let you know in four years when I'll have finished my Ph.D."


Explore further:
Genome-wide research reveals new genes involved in long-term memory

More information:
Scientific reports (2019). www.nature.com/articles/s41598-019-38939-3

Journal reference:
Scientific reports

Provided by:
University of Toronto


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