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 astir to move 3, his 4-year-old sister died of leukemia. “An quiet chamber adjacent to mine. A plaything group pinch 2 seats alternatively of one,” he said, recalling nan lingering traces of her beingness successful nan house. “There was this missing person—never spoken of—for which I had only 1 memory.” That memory, faint but enduring, was group successful nan downstairs den of their home. A young Sacktor asked his sister to publication him a book, and she brushed him off: “Go inquire your mother.” Sacktor glumly trudged up nan stairs to nan kitchen.

It’s singular that, much than 60 years later, Sacktor remembers this fleeting puerility infinitesimal astatine all. The astonishing quality of representation is that each recollection is simply a beingness trace, imprinted into encephalon insubstantial by nan molecular machinery of neurons. How nan principle of a lived infinitesimal is encoded and later retrieved remains 1 of nan cardinal unanswered questions successful neuroscience.

Sacktor became a neuroscientist successful pursuit of an answer. At nan State University of New York Downstate successful Brooklyn, he studies nan molecules progressive successful maintaining nan neuronal connections underlying memory. The mobility that has ever held his attraction was first articulated successful 1984 by nan famed biologist Francis Crick: How tin memories persist for years, moreover decades, erstwhile nan body’s molecules degrade and are replaced successful a matter of days, weeks or, astatine most, months?

In 2024, moving alongside a squad that included his longtime collaborator André Fenton, a neuroscientist astatine New York University, Sacktor offered a imaginable mentation successful a insubstantial published successful Science Advances. The researchers discovered that a persistent enslaved betwixt 2 proteins is associated pinch nan strengthening of synapses, which are nan connections betwixt neurons. Synaptic strengthening is thought to beryllium basal to representation formation. As these proteins degrade, caller ones return their spot successful a connected molecular switch that maintains nan bond’s integrity and, therefore, nan memory.

The researchers coming “a very convincing case” that “the relationship betwixt these 2 molecules is needed for representation storage,” said Karl Peter Giese, a neurobiologist astatine King’s College London who was not progressive pinch nan work. The findings connection a compelling consequence to Crick’s dilemma, reconciling nan discordant timescales to explicate really ephemeral molecules support memories that past a lifetime.

Molecular Memory

Early successful his career, Sacktor made a find that would style nan remainder of his life. After studying nether nan molecular representation pioneer James Schwartz astatine Columbia University, he opened his ain laboratory astatine SUNY Downstate to hunt for a molecule that mightiness thief explicate really semipermanent memories persist.

The molecule he was looking for would beryllium successful nan brain’s synapses. In 1949, nan scientist Donald Hebb projected that many times activating neurons strengthens nan connections betwixt them, or, arsenic nan neurobiologist Carla Shatz later put it: “Cells that occurrence together, ligament together.” In nan decades since, galore studies person suggested that nan stronger nan relationship betwixt neurons that clasp memories, nan amended nan memories persist.

In nan early 1990s, successful a crockery successful his lab, Sacktor stimulated a portion of a rat’s hippocampus—a mini region of nan encephalon linked to memories of events and places, specified arsenic nan relationship Sacktor had pinch his sister successful nan den—to activate neural pathways successful a measurement that mimicked representation encoding and storage. Then he searched for immoderate molecular changes that had taken place. Every clip he repeated nan experiment, he saw elevated levels of a definite macromolecule wrong nan synapses. “By nan 4th time, I was like, this is it,” he said.