Where do memories go when we forget: optogenetics

(ORDO NEWS) — What happens to all the information that the brain has received but not shelved? Let’s figure it out.

“Sclerosis is a wonderful disease. Nothing hurts, and every day something new. These words are attributed to the incomparable Faina Ranevskaya. Whether it was so or not, we no longer remember, but in fact, memory loss is a very unpleasant thing.

Not only for those around you, whom you no longer recognize, but also for yourself. Where did you put the keys an hour ago? Did you turn off the iron when you left the house? All problems, as a rule, begin precisely with the loss of short-term memory.

At least, this is the case with Alzheimer’s disease, the early stages of which were studied by neuroscientists from the Joint Center for Neural Genetics at the Massachusetts Institute of Technology in the United States and the RIKEN Institute for Brain Sciences in Japan.

Memory and fear

A team of researchers led by Japanese molecular biologist Suzumi Tonegawa (Nobel Prize in Physiology or Medicine 1987) studied the behavior of mice with retrograde amnesia that accompanies traumatic injury or stress.
Tonegawa and his MIT graduate student Dherai Roy and colleagues found that the mice had significant difficulty remembering things later, but were still able to remember easily in the moment. The observation led scientists to the idea that this fact can be confirmed in the early stages of Alzheimer’s disease.
They tested their guesses on two groups of genetically modified mice with symptoms of the disease, comparing them with the control.

Mice were placed in a chamber where they received an electric shock. Naturally, the animals were frightened and then fearful when they were put there again an hour later. However, when the mice again fell into this chamber a few days later, only healthy ones remembered how they “got it” here. The patients lost their fear.

Following the memories

Even before these studies, Tonegawa and his team found cells in the hippocampus that store special “memory traces.”

They were called engram cells (from the Greek “engram” – “internal record”). Scientists had an idea: is this where lost short-term memories are “hiding”? Maybe they do not disappear forever, but simply lost access to them?

Tonegawa managed to develop a line of genetically modified mice with a model of Alzheimer’s disease and at the same time modified engram cells that could be activated by laser light using optogenetics methods.

After that, neuroscientists repeated their experiment, adding another phase to it – the activation of engram cells in mice that had forgotten fear. And – about a miracle! – the fear of the current reappeared, the mice began to remember how bad they felt in this “torture chamber”.

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Scientists have also managed to understand how the loss and restoration of access to memory occurs. It’s all about neural connections. In mice with lost memories, the density of dendritic spines (the tiny extensions on neurons that connect them to each other) in engram cells was markedly lower. Stimulation restored the density of spines.

For the long memory

However, these experiments dealt with a single access to memories. What to do if you want not only to remember the past once, but also not to forget it later?

Researchers have found a solution to this problem. They were able to revive the “lost” memories for a long time, activating the formation of new connections between the entorhinal cortex and the hippocampus.

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To achieve this, the scientists used optogenetic methods to stimulate cells in the entorhinal cortex, which “feeds” engram cells in the hippocampus that encode fear memories. After three hours of the experiment, the researchers were patient and tested the mice again only a week later.

And the mice, like the hero of Arnold Schwarzenegger in the famous film, were able to “remember everything.” As expected, many more dendritic spines were found on their memory cells.

So far, it is impossible to restore human memory in this way: for this it is necessary to genetically modify memory cells directly in the brain, and the methods of laser exposure seem too crude. However, the very direction in the future therapy of lost memories has already appeared.

And perhaps some day in the future, any elderly person will be able to regain their memories with a simple and painless procedure.

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