How forgetfulness works in the brain, according to Harvard experts

Forgetting can be a blessing and a curse. Some who have experienced a traumatic event seem to be unable to forget, while others just seem to forget everything and too quickly.

Dilemmas such as these have led neuroscientists to wonder how forgetfulness actually works in the brain and whether it can be accelerated or slowed down. They are still far from understanding the process well enough to provide answers. But a group of researchers led by Harvard are getting a little closer.

In a new study, scientists who used C. elegans worms, a model organism for brain research, found that forgetting does not reverse or erase the changes in the brain that result from learning, as some theories suggest.

On the other hand, forgetfulness generates a new state of the brain that is different from that which existed before learning occurred or from that which exists while the behavior learned is still remembered. In other words, what is forgotten does not disappear completely and can be reactivated with a kind of initial jump.

“After forgetting, we can often remember what we learned before, and our brain is no longer in a naive state,” explained Yun Zhang, a professor of organic and evolutionary biology and a member of the Harvard Center for Brain Science. “If we have a party and then, several months later, we really forget: 'When did I celebrate that party? Who attended? ' And then your friend can say, 'Remember this and that. Remember that we sang a song for you. ' Suddenly, you'll remember, won't you?”

The research, published in Science Advances, sheds new light on how forgetfulness occurs in the brain at the system level and on the molecules that researchers found seem to be able to accelerate or slow it down.

The basis of the work could one day be used to understand the mental health problems in which forgetfulness goes wrong, whether it happens too slowly or too quickly. It could, for example, have keys to addressing disorders such as post-traumatic stress, where aversive memories persist aggressively.

“The mechanisms provided by this study would give us entry points to think what could have gone wrong with these neurological diseases,” Zhang said. “It helps us to make hypotheses about the molecules and processes involved, as well as the activity of neurons that are important for forgetfulness, and propose ways to understand the pathology of related neurological diseases.”

Forgetting is part of normal brain function due to the limited capacity of the brain. Much research has been done on how memories are formed, but less research has been done on the nature of forgetfulness or how it happens in the brain. Some studies suggest that when a memory is forgotten, it is simply erased and learning is lost. Another possibility is that memory and learning become more difficult to access during the process of oblivion but remain somehow.

The work of members of Zhang's laboratory, led by postdoctoral academics He Liu and Taihong Wu, and collaborators lean towards the latter theory. Researchers taught worms to identify by smell and to avoid a strain of infectious bacteria that makes them sick. But an hour later, the worms forgot. The researchers then analyzed the brain activity of these worms and the genes expressed in their nervous systems.

When compared to worms that had never learned behavior or had just finished training, the researchers saw that the neural activity and gene expression of worms that forgot the behavior did not return to the naive state of before or coincide with activity of the worms that had just been trained. They were different.

Scientists also analyzed whether worms that had forgotten training could remember it, and the answer was that it seems so. Normally, it takes three to four hours to train the worms, but those who were being retrained completed the process in about three minutes. “There are still traces of memory in his brain that can be awakened, which can be reactivated,” Zhang said.

The specialist and her colleagues plan to use this study as a starting point for further study of the mechanisms of forgetfulness and how it can eventually be applied to mental health problems. “This is just the beginning of understanding forgetfulness, an essential brain process for daily activities,” he concluded.

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