Brain Remodeling in Adolescence Temporarily Limits Access to Early Memories

A recent study in mice reveals that memories formed during adolescence may not vanish but become temporarily inaccessible as the brain undergoes structural changes. This process involves a transient weakening of protective neuronal structures, impacting the retrieval of earlier experiences.

Scientists at Albert Einstein College of Medicine investigated the retrosplenial cortex (RSP), a brain region crucial for linking memories to context and place. Their research showed that during late adolescence, perineuronal nets—mesh-like formations stabilizing neuronal connections—significantly decline in the RSP before recovering in adulthood. This temporary loss likely makes memory circuits more adaptable but also complicates access to older memories.

Unlike the RSP, the hippocampus did not exhibit similar changes, indicating that adolescent brain remodeling affects memory regions differently. The hippocampus primarily manages new memory formation, whereas the RSP supports retrieval of established memories.

How Memory Retrieval Is Affected During Brain Development

Senior author Jelena Radulovic, M.D., Ph.D., explained that the findings shed light on how adolescent brain development influences recall of earlier experiences. The observed fluctuations in perineuronal nets may prioritize memories formed in adulthood over those from early adolescence, potentially aiding adaptation to adult challenges. The team is exploring whether preventing these fluctuations during adolescence might have adverse effects later in life.

Previous assumptions held that memory circuits mature by early adolescence, but this study challenges that notion by demonstrating a late adolescent phase of instability in the RSP. This timing aligns with human brain development, which extends into the mid-to-late 20s, affecting functions such as planning and emotional regulation.

Testing Memory Stability in Adolescent Mice

To assess memory retention, researchers exposed mice to a mild foot shock in a specific chamber. Mice trained during early adolescence initially froze upon return, indicating memory of the shock, but this response diminished after several weeks. Adult-trained mice maintained freezing behavior, suggesting more stable memories.

When adolescent mice were reminded of the shock in a different environment, their fear response to the original chamber reemerged, demonstrating that the memories were stored but temporarily inaccessible. This supports the idea that adolescent memory loss is due to retrieval difficulties rather than erasure.

Role of Perineuronal Nets and Growth Factors

The team identified reduced levels of proteins essential for perineuronal net formation and maintenance, alongside decreased activity of TGFβ2, a growth factor supporting these structures, during late adolescence. Enhancing perineuronal nets or restoring TGFβ2 activity reinstated the mice's ability to retrieve earlier memories, confirming the structural changes' causal role in retrieval impairment.

By mid-adulthood, many previously inaccessible memories resurfaced without intervention, although they lacked original specificity. Mice displayed fear responses not only in the original shock chamber but also in novel settings, indicating generalized memory recall.

Why Older Memories Return Less Specific

This generalization may represent a tradeoff, where the emotional significance of an experience is retained even if exact details fade. Such broad memory retention can influence future behavior despite diminished contextual accuracy.

Researchers compared this phenomenon to the “reminiscence bump,” where adults recall numerous emotionally meaningful memories from adolescence and early adulthood, often with incomplete details. Whether both phenomena share underlying biological mechanisms remains uncertain.

Potential Implications for Psychiatric Disorders

The period of extensive brain circuit remodeling in late adolescence coincides with the typical onset of psychiatric disorders such as schizophrenia and major depression. The researchers propose that this transient instability could represent a sensitive developmental window, where genetic susceptibility combined with disruptions might elevate psychiatric risk. However, these findings are based on mouse models, and further studies are needed to confirm similar processes in humans.

The study, titled “Retrosplenial cortical reorganization during late adolescence introduces instability of contextual memory circuits,” was published on 17 July 2026 in PLOS Biology. It was supported by NIH grants R01MH108837 and R01MH078064, as well as the United States-Israel Binational Science Foundation Grant 2019261.