Researchers at Rockefeller University have uncovered a stepwise system of molecular mechanisms that helps determine how long memories persist in the brain. Using virtual reality–based learning tasks in mice, the team identified key gene regulators that stabilize important experiences over time, in findings published in Nature.
Every day, the brain turns fleeting impressions into memories that can last from minutes to years. A new study from Rockefeller University reports that this process relies on a coordinated network of molecular "timers" that guide memories from initial formation toward longer-term stability across multiple brain regions.
According to Rockefeller University and a summary in ScienceDaily, the research was led by neuroscientist Priya Rajasethupathy, head of the Skoler Horbach Family Laboratory of Neural Dynamics and Cognition. Her group has previously shown that the thalamus acts as a key relay between the hippocampus, where memories are first formed, and the cortex, where long-term memories are stored. The new work builds on that foundation by identifying gene programs that keep memories alive for progressively longer periods.
To probe these mechanisms, first author Andrea Terceros and colleagues developed a virtual reality‑based behavioral model for mice, which allowed the team to tightly control how many times animals experienced particular contexts and when they encountered them. By varying repetition, the scientists could make some experiences more memorable than others and then examine which molecular pathways were associated with memory persistence.
Co-lead author Celine Chen used a CRISPR-based screening platform to manipulate gene activity in the thalamus and cortex. As described by ScienceDaily and other outlets, this approach helped demonstrate that specific molecules do not affect whether a memory forms in the first place, but strongly influence how long it lasts.
Across these experiments, the team identified three transcriptional regulators that are critical for maintaining memories over time: Camta1 and Tcf4 in the thalamus, and Ash1l in the anterior cingulate cortex. The study reports that disrupting Camta1 and Tcf4 weakens functional connections between the thalamus and cortex and leads to memory loss.
The researchers propose a stepwise model in which memory formation begins in the hippocampus. Camta1 and its downstream targets help sustain this early trace, acting as a fast but short-lived timer. Over time, Tcf4 and its targets are activated to bolster cell adhesion and structural support, extending the lifetime of the memory. Finally, Ash1l in the cortex engages chromatin-remodeling programs that make the memory more robust and persistent.
“Unless you promote memories onto these timers, we believe you’re primed to forget it quickly,” Rajasethupathy said in comments released by Rockefeller University and quoted by several news outlets. The findings challenge older models that framed memory storage as a simple molecular on/off switch, instead portraying it as a dynamic, time-structured process.
Ash1l belongs to a family of histone methyltransferases known for preserving long-lasting “cellular memories” in other biological systems, such as immune memory and the maintenance of cell identity during development. Rajasethupathy notes that the brain may be repurposing these broadly used mechanisms to support cognitive memories.
The work also points toward potential implications for conditions such as Alzheimer’s disease. By mapping the transcriptional programs and circuits that stabilize memories, researchers hope that, in principle, future therapies might be able to route information through alternate pathways if some regions are damaged, helping healthier parts of the brain compensate.
Looking ahead, the team plans to investigate how these molecular timers are switched on and off and how the brain evaluates which experiences are important enough to be promoted along this sequence. According to ScienceDaily, their results underscore the thalamus as a central hub in deciding which memories are stabilized and for how long. The study, titled Thalamocortical transcriptional gates coordinate memory stabilization, appears in Nature (DOI: 10.1038/s41586-025-09774-6).
