Early Adolescence is a Critical Period for the Maturation of Inhibitory Behavior

Early Adolescence is a Critical Period for the Maturation of Inhibitory Behavior

Psychiatric conditions marked by impairments in cognitive control often emerge during adolescence, when the prefrontal cortex (PFC) and its inputs undergo structural and functional maturation and are vulnerable to disruption by external events. It is not known, however, whether there exists a specific temporal window within the broad range of adolescence when the development of PFC circuitry and its related behaviors are sensitive to disruption. Here we show, in male mice, that repeated exposure to amphetamine during early adolescence leads to impaired behavioral inhibition, aberrant PFC dopamine connectivity, and reduced PFC dopamine function in adulthood. Remarkably, these deficits are not observed following exposure to the exact same amphetamine regimen at later times. These findings demonstrate that there is a critical period for the disruption of the adolescent maturation of cognitive control and PFC dopamine function and suggest that early adolescence is particularly relevant to the emergence of psychopathology in humans.

以认知控制受损为特征的精神疾病往往在青春期出现，此时前额叶皮质（PFC）及其输入经历结构和功能的成熟，并且容易受到外部事件的干扰。然而，在青春期这个宽泛的时间段内，是否存在一个特定的时间窗口，在此期间PFC回路的发育及其相关行为对干扰敏感，这一点尚不清楚。在此我们发现，在雄性小鼠中，青春期早期反复接触安非他明会导致成年期行为抑制受损、PFC多巴胺连接异常以及PFC多巴胺功能降低。值得注意的是，在后期接触完全相同的安非他明方案后，并未观察到这些缺陷。这些发现表明，认知控制和PFC多巴胺功能的青春期成熟过程存在一个关键期受到干扰的阶段，并提示青春期早期与人类精神病理学的出现尤为相关。