Scientists have long known that the brain continues developing well beyond the teenage years, with important changes in decision-making, emotional regulation and memory extending into the mid-to-late 20s. Now, researchers at Albert Einstein College of Medicine have identified a biological process in mice that sheds light on how memory circuits mature during this prolonged period of brain development. Published in PLOS Biology, the study found that a key memory region undergoes a surprising phase of remodeling during late adolescence, temporarily making earlier memories harder to access before they re-emerge later in adulthood, often with less precise detail.
The researchers focused on the retrosplenial cortex (RSP), a brain region involved in organising and retrieving long-term memories. They discovered that protective, mesh-like structures known as perineuronal nets, which help stabilise memory circuits, unexpectedly diminished during late adolescence before rebuilding in adulthood. This temporary decline was observed only in the RSP and not in the nearby hippocampus, another brain region critical for memory.
According to senior author Jelena Radulovic, M.D., Ph.D., the findings provide the first detailed picture of how one of the brain’s memory circuits continues developing after adolescence. She believes the reorganisation of these protective structures may help the brain prioritise memories formed in adulthood over those from early adolescence, allowing individuals to better adapt to new challenges at different stages of life.
The timing of these changes is particularly significant because it coincides with a period now recognised as one of continued brain maturation in humans. While adolescence was once thought to end around age 19, neuroscientists increasingly acknowledge that the brain continues developing into the mid-to-late 20s. Lead author Hui Zhang, Ph.D., said the behavioural changes closely mirrored the biological ones.
As the stabilising structures in the retrosplenial cortex temporarily weakened, access to memories formed earlier in life became less reliable, suggesting that memory retrieval naturally shifts as the brain continues to mature.
To examine how these changes affected memory, the researchers trained mice to associate a particular environment with a mild foot shock. Shortly afterwards, the mice remembered the experience and froze when returned to the same location. However, weeks later, many of the mice trained during early adolescence no longer displayed the fear response, whereas mice trained in adulthood retained stable memories. When the adolescent mice were later tested in a different environment, they once again responded to the original setting, indicating that the memories had become temporarily inaccessible rather than erased.
Further analysis revealed that the temporary loss of memory access was linked to reduced levels of proteins that maintain perineuronal nets, along with lower activity of TGFβ2, a growth factor that supports these protective structures. When researchers restored either the perineuronal nets or TGFβ2 activity, the mice regained access to memories formed earlier in life. By mid-adulthood, many of these memories returned naturally, although they were less specific, with the mice responding similarly in unfamiliar environments. The researchers note that this resembles the “reminiscence bump” seen in humans, in which adults tend to recall experiences from adolescence and early adulthood more readily than memories from other periods of life, while often remembering their emotional significance more clearly than the exact details.
Beyond advancing understanding of memory, the findings may also provide clues about mental health. Schizophrenia and major depression frequently emerge during late adolescence, the same developmental stage in which the researchers observed extensive remodeling of memory circuits in mice. The team suggests that disruptions to this normal developmental process could contribute to vulnerability to psychiatric disorders in genetically susceptible individuals. Although further studies are needed to determine whether the same mechanisms operate in people, the research offers an important new perspective on how the developing brain reshapes memories while preparing for adulthood.
More information: Hui Zhang et al, Retrosplenial cortical reorganization during late adolescence introduces instability of contextual memory circuits, PLOS Biology. DOI: 10.1371/journal.pbio.3003908
Journal information: PLOS Biology Provided by Albert Einstein College of Medicine
