How the union of two brain molecules produces memory that lasts for a lifetime

Original version of This story Appear in Quanta Magazine.

When Todd Sacktor was about to turn 3, his 4-year-old sister died of leukemia. “A empty bedroom next to me. A swing with two seats,” he said, recalling her lingering traces of the house. “There is a missing person-never said, because I only have one memory.” This memory is faint but lasting, set in the downstairs nest of their home. A young sack asked his sister to study for him, and she wiped him: “Go and ask your mom.” Sacktor drowsyly climbed up the stairs to the kitchen.

It is worth noting that over 60 years later, Sacktor fully remembers this short childhood moment. The amazing nature of memory is that every memory is a physical trace, which is mechanically printed in the brain tissue through the molecular mechanical of neurons. How the nature of life moments is coded, what is later retrieved remains one of the unsolved central problems in neuroscience.

Sacktor becomes a neuroscientist who pursues answers. At SUNY, Brooklyn, he studied molecules involved in maintaining neuronal connections. The question that has always attracted his attention was first explained in 1984 by the famous biologist Francis Crick: When molecules in the human body degrade and in days, weeks, weeks, most months, how can memories last for years, or even decades?

Working with a team in 2024, including his longtime collaborator André Fenton, neuroscientist André Fenton at New York University, Sacktor provides potential explanations in a published paper. Science Advances. The researchers found that the sustained bond between the two proteins is related to the strengthening of synapses, which are the link between neurons. Synaptic enhancement is considered to be the basis of memory formation. As these proteins decrease, new proteins place them in the interchange of linked molecules, which maintain the integrity of the bond and thus is memory.

The researchers have proposed “a very compelling case” that memory storage requires interactions between these two molecules,” said Karl Peter Giese, a neurobiologist at King’s College London. These findings provide a compelling response to Crick’s plight and check inconsistent timelines to explain how ephemeral molecules maintain memory that lasts a lifetime.

Molecular memory

Early in his career, Sacktor discovered a discovery that shaped the rest of his life. After studying at James Schwartz, a pioneer in molecular memory at Columbia University, he opened his own lab at Suny Downstate to find molecules that can help explain long-term memory.

The molecules he is looking for will be in the synapses of the brain. In 1949, psychologist Donald Hebb proposed that repetitive activation of neurons can strengthen their connection, or, as neurobiologist Carla Shatz later said, “Start it, connect it together.” In the decades since, many studies have shown that the stronger the connection between neurons with memory, the more persistent the memory.

In the early 1990s, in a dish in his lab, Sacktor stimulated a slice of rat hippocampus, a small area of ​​the brain associated with memory of events and places, such as interactions with his sister in Den, activate neural pathways in a way that mimics memory and storage. He then searches for any molecular changes that occur. Each time he repeated the experiment, he would see an increase in the level of a certain protein in his synapses. He said, “By the fourth time, I think, that’s it.”