Some memories from adolescence may not disappear. The brain may simply lock them away for a time while its memory system is being rebuilt.
A study in mice has uncovered an unexpected wave of remodeling in a brain region that helps preserve and retrieve long-term memories. During late adolescence, the protective structures surrounding key neurons temporarily weakened, making experiences from earlier life harder to recall. Those memories often returned in adulthood, but some had lost their original precision.
The findings, published in PLOS Biology by researchers at Albert Einstein College of Medicine, offer a possible biological explanation for why access to older memories can shift as the brain matures. They also reinforce the idea that adolescence is not a brief transition that ends with the teenage years but a prolonged period in which neural circuits continue to reorganize.
A Memory Circuit Under Reconstruction
The researchers focused on the retrosplenial cortex (RSP), an area that helps connect experiences with places, context, and previously stored information. Although it receives less public attention than the hippocampus, the RSP is an important part of the network the brain uses to retrieve established memories.
In late adolescent mice, the team found that perineuronal nets in the RSP declined sharply before recovering in adulthood. These mesh-like structures form around certain neurons and help stabilize the connections that preserve information over time. Their temporary loss may make memory circuits more flexible, but it may also make older memories more difficult to access.
The same changes did not occur in the nearby hippocampus, which is strongly involved in forming and organizing new memories. That regional difference suggests that adolescence does not reshape every part of the memory system in the same way.
Why Memory Access Temporarily Changes
“We’ve known for years that the brain continues developing through adolescence and young adulthood,” said senior author Jelena Radulovic, M.D., Ph.D., professor in the Dominick P. Purpura Department of Neuroscience and of psychiatry and behavioral sciences at Einstein.
“Our findings begin to explain what that developmental process looks like in one of the brain’s memory circuits and how it can influence the way earlier experiences are recalled.
“We do not yet fully understand the consequences of the observed fluctuations of perineuronal nets, but we believe that their reorganization in RSP helps prioritize access to memories formed in adulthood at the expense of those formed in early adolescence. This could help to better adapt to the circumstances and challenges encountered during adult life stages.
“We are investigating whether preventing such fluctuations in adolescence would have any negative consequences in later life.”
Adolescence Lasts Longer Than Expected
Earlier studies had suggested that the memory circuits examined by the team were largely mature by early adolescence. The new results challenge that view. Rather than remaining stable, an important part of the system appears to enter a temporary period of instability later in adolescence before settling again in adulthood.
That timing is especially relevant because the human brain also continues developing well beyond the teenage years. Processes involved in planning, impulse control, emotional regulation, and decision-making can continue maturing into the mid-to-late 20s. According to the National Institutes of Health, the brain remains underdeveloped during this extended period.
“The behavior matched the biology,” said lead author Hui Zhang, Ph.D., a research fellow at Einstein. “The retrosplenial cortex is responsible for older, more established memories. As its stabilizing structures declined, access to memories formed earlier in life became less reliable.”
Memories Became Hidden, Not Erased
To test the effects on memory, the researchers placed mice in a chamber where they received a mild foot shock. When returned shortly afterward, the animals froze, showing that they remembered the unpleasant experience.
The response changed with time. Many mice trained during early adolescence stopped freezing when they were returned to the chamber several weeks later. Adult mice trained in the same way continued to respond, indicating that their memories remained more stable.
The adolescent memories had not been erased. When the mice were reminded of the unpleasant event in a different setting, their fear of the original chamber returned. The experiment showed that the information was still stored but had become temporarily difficult to retrieve.
Restoring the Brain’s Protective Nets
The researchers linked this loss of access to reduced levels of proteins needed to build and maintain perineuronal nets. Activity of TGFβ2, a growth factor that supports those structures, also fell during the same period.
When the team strengthened the nets or restored TGFβ2 activity, the animals again became able to retrieve memories formed earlier in life. That result provided direct evidence that the structural changes were not merely associated with memory loss but were helping cause the retrieval problem.
By mid-adulthood, many of the inaccessible memories returned without intervention. However, they were no longer as specific. Instead of reacting only to the chamber where the shock occurred, the mice also showed fear in unfamiliar environments.
Why Old Memories Return Blurred
Such generalization may reflect a tradeoff. Remembering the broad emotional lesson of an experience can be useful even when its precise context has faded. A dangerous encounter, for example, may shape future behavior even if the details of where and when it happened become blurred.
The researchers compared this pattern with the “reminiscence bump,” the tendency for adults to recall an unusually large number of memories from adolescence and early adulthood. Those memories often retain strong emotional meaning even when their finer details are incomplete.
Whether the two phenomena are driven by the same biology remains unknown. The researchers say the later return of adolescent memories could result from an age-related increase in perineuronal nets, repeated exposure to similar experiences, the replay of old events, or another process that has yet to be identified.
A Possible Window of Psychiatric Vulnerability
Schizophrenia and major depression frequently emerge during late adolescence, which overlaps with the period of extensive circuit remodeling observed in the mice.
The researchers suggest that this temporary instability may create a sensitive developmental window. In people with a genetic susceptibility, disruptions to the process could potentially increase the risk of psychiatric illness. However, the experiments were conducted in mice, and further research will be needed to establish whether human memory circuits undergo the same changes.
Reference: “Retrosplenial cortical reorganization during late adolescence introduces instability of contextual memory circuits” by Hui Zhang, Zorica Petrovic, Elizabeth M. Wood, Ana Cicvaric, Maayan Krispil-Alon, Vladimir Jovasevic, Kendra Parker, Thomas E. Bassett, Anna Carboncino, Anita L. Guedea, Pengfei Yi, Gal Richter-Levin, J. Tiago Gonçalves and Jelena Radulovic, 17 July 2026, PLOS Biology.
DOI: 10.1371/journal.pbio.3003908
The paper was supported by NIH grants R01MH108837 and R01MH078064 and the United States-Israel Binational Science Foundation Grant 2019261.
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