Researchers at Albert Einstein College of Medicine have identified a biological process in mice that sheds new light on how memory circuits mature during adolescence, according to a study published July 17 in PLOS Biology. The study found that the retrosplenial cortex, a key memory region of the mouse brain, undergoes an unexpected period of remodeling during late adolescence. During this time, memories formed earlier in life become temporarily harder to retrieve but can resurface later with less precise detail.
The researchers focused on perineuronal nets—protective mesh-like structures that stabilize memory circuits—and discovered these nets diminished during late adolescence before rebuilding in adulthood. These changes were specific to the retrosplenial cortex and did not occur in the nearby hippocampus. "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 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." Radulovic also said, "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 at different life stages." She added, "Whether remembering early adolescent experiences comes at the cost of adjusting to new ones is a possibility that we are currently investigating."
Previous studies suggested these memory circuits matured by early adolescence; however, this research found an important stabilizing system temporarily weakened during late adolescence before recovering later on. The timing aligns with what neuroscientists now recognize as continued human brain maturation into one's mid-to-late 20s.
To assess behavioral effects, scientists trained mice to associate a specific environment with a mild foot shock. While adolescent mice initially remembered and reacted fearfully when returned shortly after training, weeks later many no longer showed this response—unlike adult-trained mice who retained stable memories over time. When retested later under different conditions, adolescent-trained mice responded again to original settings, indicating their memories had become inaccessible rather than erased.
Further investigation traced these changes back to reduced structural proteins supporting perineuronal nets and lower activity from TGFβ2—a growth factor involved with maintaining those structures. Reinforcing these networks or restoring TGFβ2 allowed retrieval of previously inaccessible memories.
By mid-adulthood many lost memories resurfaced spontaneously but became less precise: instead of responding only to original environments where fear was learned, mice generalized their response more broadly—a pattern resembling adults’ tendency for emotional recall over specific details from youth experiences (the so-called 'reminiscence bump'). Researchers note whether this effect results from random increases or experience-driven boosts in perineuronal nets remains unclear.
The authors suggest implications may extend beyond memory alone; since psychiatric disorders like schizophrenia often emerge during late adolescence—the same window when remodeling was observed—alterations here could contribute vulnerability among genetically susceptible individuals, though further research is needed.
