Memory Shaped by Brain Remodeling During Adolescence in Mice

The human brain continues developing beyond the teenage years, with crucial changes involving decision-making and emotional regulation extending into the mid-to-late 20s. Researchers at Albert Einstein College of Medicine have identified a biological process in mice that offers new insight into how memory circuits mature during this period of brain development. 

The study published in PLOS Biology titled, “Retrosplenial cortical reorganization during late adolescence introduces instability of contextual memory circuits,” found that a key memory region of the mouse brain undergoes a period of remodeling during late adolescence, causing memories formed earlier in life to become temporarily more difficult to retrieve before resurfacing with less precise detail. The findings identify a biological mechanism that may explain how access to memories changes during development. 

The study focused on the retrosplenial cortex (RSP) and discovered that protective mesh-like structures, called perineuronal nets, stabilize memory circuits and unexpectedly diminish during late adolescence before rebuilding in adulthood. The changes were confined to the RSP and were not observed in the nearby hippocampus, another brain region essential for memory. 

“We’ve known for years that the brain continues developing through adolescence and young adulthood,” said senior author Jelena Radulovic, MD, PhD, professor of neuroscience, 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. 

Previous studies suggested that the memory circuits reached maturity during early adolescence. Instead, results showed that an important stabilizing system temporarily weakened during late adolescence before recovering in adulthood. 

The timing is notable because it corresponds to a period now recognized as one of continued brain maturation in humans. According to the National Institutes of Health, the brain continues developing and maturing into the mid-to-late 20s. 

“The behavior matched the biology,” said lead author Hui Zhang, PhD, 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.” 

To determine how these brain changes affected behavior, the researchers trained mice to associate a specific environment with a mild foot shock. The mice remembered the experience and froze when returned to the same chamber. Weeks later, many of the mice trained during early adolescence no longer showed that fear response, while mice trained during adulthood retained stable memories over the same period. 

When the adolescent mice later experienced another test in a different environment, they once again responded to the original setting, demonstrating that the memories had become temporarily inaccessible rather than erased. 

The researchers traced these changes to a decline in key structural proteins that help build and maintain perineuronal nets, along with reduced activity of growth factor, TGFβ2. When TGFβ2 activity was restored, the mice regained their ability to retrieve memories formed earlier in life. 

By mid-adulthood, many of those memories resurfaced spontaneously, although they had become less precise. Rather than responding only to the original environment, the mice generalized their fear to unfamiliar settings. The researchers note that this pattern resembles the “reminiscence bump,” a well-known phenomenon in which adults disproportionately recall memories from adolescence and early adulthood while often remembering the emotional significance of an experience more readily than its specific details.  

The findings may also have implications beyond memory. Schizophrenia and major depression often emerge in humans during late adolescence. The authors suggest that changes in this developmental process could contribute to vulnerability to psychiatric disorders in genetically susceptible individuals. Additional research is needed to evaluate whether similar mechanisms occur in humans. 

The post Memory Shaped by Brain Remodeling During Adolescence in Mice appeared first on GEN - Genetic Engineering and Biotechnology News.