How the Binding of Two Brain Molecules Creates Memories That Last a Lifetime

The archetypal version of this story appeared in Quanta Magazine.

When Todd Sacktor was astir to crook 3, his 4-year-old sister died of leukemia. “An bare chamber adjacent to mine. A plaything acceptable with 2 seats alternatively of one,” helium said, recalling the lingering traces of her beingness successful the house. “There was this missing person—never spoken of—for which I had lone 1 memory.” That memory, faint but enduring, was acceptable successful the downstairs den of their home. A young Sacktor asked his sister to work him a book, and she brushed him off: “Go inquire your mother.” Sacktor glumly trudged up the stairs to the 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 carnal trace, imprinted into encephalon insubstantial by the molecular machinery of neurons. How the essence of a lived infinitesimal is encoded and aboriginal retrieved remains 1 of the cardinal unanswered questions successful neuroscience.

Sacktor became a neuroscientist successful pursuit of an answer. At the State University of New York Downstate successful Brooklyn, helium studies the molecules progressive successful maintaining the neuronal connections underlying memory. The question that has ever held his attraction was first articulated successful 1984 by the famed biologist Francis Crick: How tin memories persist for years, adjacent decades, erstwhile the body’s molecules degrade and are replaced successful a substance 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 with the strengthening of synapses, which are the connections betwixt neurons. Synaptic strengthening is thought to beryllium cardinal to representation formation. As these proteins degrade, caller ones instrumentality their spot successful a connected molecular swap that maintains the bond’s integrity and, therefore, the memory.

The researchers contiguous “a precise convincing case” that “the enactment betwixt these 2 molecules is needed for representation storage,” said Karl Peter Giese, a neurobiologist astatine King’s College London who was not progressive with the work. The findings connection a compelling effect to Crick’s dilemma, reconciling the discordant timescales to explicate however ephemeral molecules support memories that past a lifetime.

Molecular Memory

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

The molecule helium was looking for would beryllium successful the brain’s synapses. In 1949, the scientist Donald Hebb projected that repeatedly activating neurons strengthens the connections betwixt them, or, arsenic the neurobiologist Carla Shatz aboriginal enactment it: “Cells that occurrence together, ligament together.” In the decades since, galore studies person suggested that the stronger the transportation betwixt neurons that clasp memories, the amended the memories persist.

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