During adolescence, the prefrontal cortex (PFC) undergoes dramatic reorganization. PFC development is profoundly influenced by the social environment, disruptions to which may prime the emergence of psychopathology across the lifespan. We investigated the neurobehavioral consequences of isolation experienced in adolescence in mice, and in particular, the long-term consequences that were detectable even despite normalization of the social milieu. Isolation produced biases toward habit-like behavior at the expense of flexible goal seeking, plus anhedonic-like reward deficits. Behavioral phenomena were accompanied by neuronal dendritic spine over-abundance and hyper-excitability in the ventromedial PFC (vmPFC), which was necessary for the expression of isolation-induced habits and sufficient to trigger behavioral inflexibility in socially reared controls. Isolation activated cytoskeletal regulatory pathways otherwise suppressed during adolescence, such that repression of constituent elements prevented long-term isolation-induced neurosequelae. Altogether, our findings unveil an adolescent critical period and multi-model mechanism by which social experiences facilitate prefrontal cortical maturation.

在青春期，前额叶皮层（PFC）经历戏剧性的重组。 PFC 的发展深受社会环境的影响，社会环境的破坏可能会导致整个生命周期中精神病理学的出现。我们研究了小鼠青春期经历的隔离的神经行为后果，特别是即使社会环境正常化但仍可检测到的长期后果。孤立导致了对类似习惯的行为的偏见，但牺牲了灵活的目标寻求，加上快感缺乏的奖励赤字。行为现象伴随着腹内侧前额皮层（vmPFC）的神经元树突棘过度丰富和过度兴奋，这对于表达隔离诱导的习惯是必要的，并且足以引发社会养育的对照组的行为僵化。隔离激活了青春期期间被抑制的细胞骨架调节途径，因此对组成元素的抑制可以防止长期隔离引起的神经后遗症。总而言之，我们的研究结果揭示了青少年关键期和社会经历促进前额皮质成熟的多模式机制。