How the Binding of Two Brain Molecules Creates Memories That Last a Lifetime
The original version of This story appeared in Quanta Magazine.
When Todd Sacktor was about to be 3 years old, his 4 -year -old sister died of leukemia. “An empty room next to mine. A swing with two seats instead of one,” he said, recalling the persistent traces of his presence in the house. “There was this missing person – who never talked about – for whom I had only one memory.” This souvenir, light but durable, was located in the lair at the bottom of their house. A young bag asked her sister to read him a book, and she pushed him back: “Go ask your mother.” Sacktor scolded the stairs to the kitchen.
It is remarkable that, more than 60 years later, Sacktor remembers this ephemeral moment of childhood. The astonishing nature of memory is that each memory is a physical trace, printed in the cerebral fabric by the molecular machinery of neurons. How the essence of a lived moment is coded and recovered later remains one of the central questions unanswered in neuroscience.
Sacktor has become a neuroscientist looking for an answer. At New York State University, northern Brooklyn State, he studied the molecules involved in maintaining the underlying neural connections. The question that has always caught his attention was exposed for the first time in 1984 by the famous biologist Francis Crick: how can memories persist for years, even decades, when the molecules of the body deteriorate and are replaced in a few days, weeks or, at most, months?
In 2024, working alongside a team that included his longtime employee André Fenton, neuroscientist at New York University, Sacktor offered a potential explanation in an article published in Scientific advances. The researchers discovered that a persistent link between two proteins is associated with the strengthening of synapses, which are the connections between neurons. It is believed that synaptic strengthening is fundamental for the formation of memory. As these proteins deteriorate, the news takes their place in a connected molecular exchange which maintains the integrity of the link and, therefore, the memory.
The researchers present “a very convincing case” that “the interaction between these two molecules is necessary for the storage of memory,” said Karl Peter Giese, neurobiologist at King’s College in London who was not involved in the work. The results offer a convincing response to the Dilemma of Crick, reconciling the discordant time scales to explain how ephemeral molecules maintain memories which last a lifetime.
Molecular memory
At the start of his career, Sacktor made a discovery that would shape the rest of his life. After studying under the pioneer of James Schwartz molecular memory at Columbia University, he opened his own laboratory in Suny Downnstate to seek a molecule that could help explain how long -term memories persist.
The molecule he was looking for would be in brain synapses. In 1949, psychologist Donald Hebb proposed that the neurons activating several times reinforce the links between them, or, as the neurobiologist Carla Shatz later: “cells that were pulled together, wandered together”. During the decades that have followed, many studies have suggested that the more the neurons that will hold memories, the better the memories persist.
In the early 1990s, in a dish of his laboratory, Sacktor stimulated a hippocampal slice of a rat – a small region of the brain linked to memories of events and places, such as interaction, Sacktor had with his sister in the den – to activate the neuronal ways in a way that imitated memory and the storage of memory. Then he looked for molecular changes that had taken place. Whenever he repeated the experience, he saw high levels of a certain protein in synapses. “In the fourth time, I said to myself, that’s it,” he said.
