Molecular Mechanisms Determine Which Memories Last in the Brain
- Ritambhara K
- 6 hours ago
- 3 min read
Every day, our brains transform fleeting impressions, sudden flashes of inspiration, and even painful experiences into lasting memories that shape our sense of self and guide how we navigate the world. But how does the brain decide which experiences are worth remembering—and for how long?
A new study reveals that long-term memory is orchestrated by a cascade of molecular timers distributed across multiple brain regions. Using a virtual reality-based behavioral model in mice, researchers discovered that memories are either promoted into progressively more enduring forms or demoted until they fade, depending on the action of key molecular regulators. These findings, published in Nature, highlight the brain’s remarkable ability to assess the importance of experiences and gradually reorganize memories for long-term storage.
“This is a key revelation because it explains how we adjust the durability of memories,” says Priya Rajasethupathy, head of the Skoler Horbach Family Laboratory of Neural Dynamics and Cognition. “What we choose to remember is a continuously evolving process rather than a one-time flip of a switch.”
Beyond Hippocampus and Cortex
For decades, memory research focused primarily on two brain regions: the hippocampus, associated with short-term memory, and the cortex, thought to house long-term memories. Earlier models likened memory to transistor-like switches—once a short-term memory was marked for long-term storage, it was assumed to persist indefinitely. Yet such models could not explain why some memories last a lifetime while others vanish within weeks.
In 2023, Rajasethupathy and colleagues identified a critical pathway linking short- and long-term memories, highlighting the role of the thalamus. This central brain region not only selects which memories should persist but routes them to the cortex for stabilization, setting the stage for understanding how experiences are selectively retained or forgotten.
Virtual Reality Unlocks Memory Mechanisms
To probe this process, the team developed a virtual reality system where mice formed specific memories. By varying the repetition of certain experiences, the researchers observed which memories persisted longer and examined the molecular mechanisms behind their durability.
WATCH ALSO: https://www.modernmechanics24.com/post/an-unmanned-boat-has-completed-a-long-1-100-nautical-mile-voyage
Postdoctoral researcher Andrea Terceros created the behavioral model, while co-lead Celine Chen developed a CRISPR-based platform to manipulate genes in the thalamus and cortex. This allowed the team to demonstrate causality: removing certain molecules directly affected the duration of memory.
Molecular Timers Govern Memory Persistence
The study revealed that long-term memory is maintained not by a single molecular switch, but by a series of gene-regulating timers unfolding across time and brain regions. Early timers act quickly and fade, enabling rapid forgetting, while later timers act more slowly to create durable memories.
By using repetition as a proxy for importance, the researchers identified three transcriptional regulators crucial for memory maintenance: Camta1 and Tcf4 in the thalamus, and Ash1l in the anterior cingulate cortex. Camta1 supports initial persistence, Tcf4 reinforces structural connections, and Ash1l recruits chromatin-remodeling programs to solidify memories long-term.
“These molecular timers help the brain prioritize which experiences should endure,” explains Rajasethupathy. Interestingly, Ash1l belongs to a family of proteins involved in other biological forms of memory, such as immune system responses and cell identity during development, suggesting that the brain repurposes existing cellular memory mechanisms for cognitive memory.
Implications for Memory Disorders
The discovery has potential applications for memory-related diseases like Alzheimer’s. By mapping the molecular pathways that preserve memory, scientists may eventually develop ways to route memories around damaged brain regions, allowing healthy circuits to take over.
Rajasethupathy’s lab is now focused on understanding how these molecular timers are activated and what determines the lifespan of a memory. “We’re interested in understanding the life of a memory beyond its initial formation in the hippocampus,” she says. “The thalamus and its communication with the cortex appear central to this process.”
Comments