Adolescence is a period of enormous change. We learn how to navigate increasingly complicated social relationships, become more independent, and develop many of the cognitive abilities we will rely on throughout adulthood. At the same time, the brain is still changing. Connections between the hippocampus, which plays an important role in memory, and the prefrontal cortex, which helps regulate cognition and behavior, continue to mature during adolescence. Inhibitory circuits that help coordinate activity across these brain regions are also still developing. That raises an important question—What happens when the social environment is repeatedly disrupted during this period?
Recent research in mice at USC suggests that the consequences can persist long after the instability itself has ended. Researchers found that disrupting social stability during adolescence was associated with a specific memory impairment in adulthood, along with changes in the organization and coordination of brain circuits involved in cognition.
Creating social instability: To study this question, the team used a model called social instability stress, or SIS. Mice normally establish stable social groups. In the experiment, control mice remained with the same cage mates. For the SIS group, however, they changed their cage mates twice each week for seven weeks during adolescence. Just as a social group could become familiar, they disrupted it and created a new one. They then asked what consequences this adolescent experience might have for the brain and behavior. One of the clearest effects involved recognition memory, the ability to distinguish something familiar from something new. When adult mice encountered an object they had seen before alongside a new object, control mice spent more time investigating the novel object. Mice that had experienced adolescent social instability did not show the same preference. What made this particularly interesting was what they didn't find. Specifically, SIS mice did not show significant differences in anxiety. They also showed normal social preference and no significant impairment on an object-location memory task. Therefore, the effect is not a generalized behavioral disruption. Instead, social instability appeared to leave a more selective mark on recognition memory.
The memory problem had a neural signature: While mice performed the recognition-memory task, the researchers recorded electrical activity from several regions of the hippocampus and prefrontal cortex. Rather than simply asking whether individual brain regions were more or less active, they asked how effectively different regions were communicating with one another. Neurons generate rhythmic patterns of electrical activity, and populations of neurons in different regions can synchronize these rhythms. One way of measuring that coordination is called coherence. In mice exposed to adolescent social instability, high-frequency coherence between two hippocampal regions, called CA3 and CA1, was significantly reduced during the recognition-memory task. That finding is intriguing because communication between CA3 and CA1 is thought to contribute to memory processing. Previous work has shown that high-frequency synchrony increases as animals investigate novel objects or locations. The results therefore raise the possibility that adolescent social instability does not simply change activity in one part of the brain, it may alter how effectively components of a memory network coordinate their activity.
A change in the brain's inhibitory circuitry: The group also found clues in structures called perineuronal nets, or PNNs. PNNs are specialized structures that form around certain neurons, particularly fast-spiking inhibitory neurons containing the protein parvalbumin. They help regulate synaptic stability, neuronal excitability, and plasticity. Their development is also associated with the closing of sensitive periods in the developing brain. Social instability did not reduce the overall number of these parvalbumin-containing neurons. Instead, it selectively reduces the proportion surrounded by PNNs in the prefrontal cortex. Similar changes did not occur in the CA1 or CA3 regions of the hippocampus. One possibility is that this leaves prefrontal inhibitory circuits in a more plastic, or less stable state. But that interpretation remains a hypothesis. The study identifies associations between adolescent social instability, PNN organization, neural coordination, and adult memory; it does not establish that one of these changes causes the others.
Future Directions: These findings point toward a larger idea: the social environment experienced during adolescence may help shape how brain circuits mature. In mice, repeatedly disrupting social stability during this developmental window was followed by changes that remained detectable in adulthood, not as a broad disruption of behavior or brain activity, but as a more specific combination of impaired recognition memory, altered hippocampal communication, and changes in inhibitory-circuit organization. The team next wants to understand how these pieces fit together. For example, when do the neural changes first emerge? What mechanisms cause perineuronal nets to change? And, perhaps most importantly, could restoring inhibitory circuit organization also restore normal patterns of neural communication and memory among adults who experience unstable relationships in adolescence? Understanding that interaction may eventually help explain how experiences during adolescence can leave biological traces that last long after the experience itself is over.