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Mechanism found to determine which memories last

In recent decades, neuroscientists have established the idea that some of the experiences of each day are converted by the brain into permanent memories during sleep that same night. Now, a new study proposes a mechanism that determines which memories are labeled as important enough to remain in the brain until sleep makes them permanent.

Led by researchers at New York University Grossman School of Medicine, the study revolves around brain cells called neurons that “switch on” (or cause changes in the balance of their positive and negative charges) to transmit electrical signals that They encode memories. Large groups of neurons in a brain region called the hippocampus fire together in rhythmic cycles, creating sequences of signals within milliseconds of each other that can encode complex information.

Called “sharp waves,” these “screams” to the rest of the brain represent the nearly simultaneous activation of 15 percent of the neurons in the hippocampus, and are named for the shape they take when their activity is captured by electrodes and recorded on a graph. .

While previous studies have linked the waves to the formation of memories during sleep, the new study, published online in the journal Science on March 28, they found that daytime events immediately followed by between five and 20 sharp waves are repeated more during sleep and are therefore consolidated into permanent memories. Events followed by very few or no sharp waves failed to form lasting memories.

“Our study finds that sharp waves are the physiological mechanism used by the brain to ‘decide’ what to keep and what to discard,” said study senior author György Buzsáki, MD, PhD, Biggs Professor of Neuroscience in the Department of Neuroscience and Neuroscience. Physiology at NYU Langone Health.

Walk and pause

The new study builds on a known pattern: Mammals, including humans, experience the world for a few moments, then pause, then experience some more, then pause again. After paying attention to something, the study authors say, the brain’s calculation often switches to an “inactive” reappraisal mode. These momentary pauses occur throughout the day, but longer periods of inactivity occur during sleep.

Buzsaki and his colleagues had previously established that sharp waves do not occur while we are actively exploring sensory information or moving, but only during inactive pauses before or after. The current study found that sharp waves represent the natural labeling mechanism during such pauses after waking experiences, with the labeled neural patterns reactivated during post-task sleep.

Importantly, sharp waves are known to be formed by activating “place cells” in the hippocampus in a specific order that encodes each room we enter and each arm of a maze a mouse enters. For memories that are recalled, those same cells activate at high speed, while we sleep, “replaying the recorded event thousands of times per night.” The process strengthens the connections between the cells involved.

For the current study, successive maze runs performed by study mice were tracked using electrodes using hippocampal cell populations that constantly changed over time despite recording very similar experiences. This revealed for the first time maze runs during which waves were produced during waking pauses and then repeated during sleep.

Sharp waves were typically recorded when a mouse stopped to enjoy a sugary snack after each run through the maze. Consumption of the reward, the authors say, primed the brain to switch from an exploratory pattern to an inactive one, so that sharp waves could occur.

Using double-sided silicon probes, the research team was able to record up to 500 neurons simultaneously in the hippocampus of animals as they ran the maze. This, in turn, created a challenge because the data becomes extremely complex the more neurons are recorded independently. To gain an intuitive understanding of the data, visualize neural activity, and formulate hypotheses, the team successfully reduced the number of dimensions of the data, somewhat like converting a three-dimensional image into a flat one, and without losing the integrity of the data. . .

“We worked to remove the external world from the equation and looked at the mechanisms by which the mammalian brain innately and subconsciously marks some memories so that they become permanent,” said first author Wannan (Winnie) Yang, PhD, student postgraduate in Buzsáki. laboratory. “Why such a system evolved remains a mystery, but future research may reveal devices or therapies that can tune sharp waves to improve memory, or even decrease recall of traumatic events.”

Along with Drs. Buzsáki and Yang, the authors of the study from the NYU Langone Health Neuroscience Institute were Roman Huszár and Thomas Hainmueller. Kirill Kiselev of New York University’s Center for Neural Sciences was also an author, as was Chen Sun of Mila, the Quebec Institute of Artificial Intelligence, in Montreal. The work was supported by National Institutes of Health grants R01MH122391 and U19NS107616.