Persistent behavioral and neurobiological consequences of social isolation during adolescence

Abstract

Meaningful social interactions are a fundamental human need, the lack of which can pose serious risks to an individual's physical and mental health. Across species, peer-oriented social behaviors are dramatically reshaped during adolescence, a developmental period characterized by dynamic changes in brain structure and function as individuals transition into adulthood. Thus, the experience of social isolation during this critical developmental stage may be especially pernicious, as it could permanently derail typical neurobiological processes that are necessary for establishing adaptive adult behaviors. The purpose of this review is to summarize investigations in which rodents were isolated during adolescence, then re-housed in typical social groups prior to testing, thus allowing the investigators to resolve the long-term consequences of social adversity experienced during adolescent sensitive periods, despite subsequent normalization of the social environment. Here, we discuss alterations in social, anxiety-like, cognitive, and decision-making behaviors in previously isolated adult rodents. We then explore corresponding neurobiological findings, focusing on the prefrontal cortex, including changes in synaptic densities and protein levels, white matter and oligodendrocyte function, and neuronal physiology. Made more urgent by the recent wave of social deprivation resulting from the COVID-19 pandemic, especially amongst school-aged adolescents, understanding the mechanisms by which even transient social adversity can negatively impact brain function across the lifespan is of paramount importance.

Keywords: Adolescent; Adversity; Orbitofrontal; Prefrontal; Stress.

Figure 1.. Illustration of instrumental tasks used to assess goal-directed decision making.

In both tasks, animals are first trained to associate two actions (left vs. right nose-pokes) with delivery of two distinct reinforcers (yellow vs. grey pellets). (A) Illustration of outcome devaluation. Immediately prior to a choice test, animals are allowed to freely consume one of two the pellets (e.g. grey pellet) thus decreasing the value of that outcome. (B) Choice test responding whereby goal-directed action is defined by a preference for the nose-poke aperture associated with the valued vs. devalued pellet. (C) Illustration of contingency degradation. Animals undergo a session in which one action (e.g. nose-poking on the left) is reinforced as during training, while the other action (e.g. nose-poking on the right) is no longer linked to reinforcer deliver and instead the pellet associated with that action (e.g. grey pellet) is non-contingently (or “for free”). (D) Choice test responding whereby goal-directed action is defined by a preference for the nose-poke aperture associated with the previously reinforced vs. degraded contingency.