Impaired cortical maturation is a postulated mechanism in the etiology of neurodevelopmental disorders, including schizophrenia. In the sensory cortex, activity relayed by the thalamus during a postnatal sensitive period is essential for proper cortical maturation. Whether thalamic activity also shapes prefrontal cortical maturation is unknown. We show that inhibiting the mediodorsal and midline thalamus in mice during adolescence leads to a long-lasting decrease in thalamo–prefrontal projection density and reduced excitatory drive to prefrontal neurons. It also caused prefrontal-dependent cognitive deficits during adulthood associated with disrupted prefrontal cross-correlations and task outcome encoding. Thalamic inhibition during adulthood had no long-lasting consequences. Exciting the thalamus in adulthood during a cognitive task rescued prefrontal cross-correlations, task outcome encoding and cognitive deficits. These data point to adolescence as a sensitive window of thalamocortical circuit maturation. Furthermore, by supporting prefrontal network activity, boosting thalamic activity provides a potential therapeutic strategy for rescuing cognitive deficits in neurodevelopmental disorders.

皮质成熟受损是神经发育障碍（包括精神分裂症）病因学中的一种假设机制。在感觉皮层中，丘脑在产后敏感期传递的活动对于皮质的正常成熟至关重要。丘脑活动是否也会影响前额皮质的成熟尚不清楚。我们发现，在青春期抑制小鼠的丘脑内侧和中线会导致丘脑-前额叶投射密度的长期下降，并减少对前额叶神经元的兴奋性驱动。它还在成年期间导致前额叶依赖性认知缺陷，与前额叶互相关性和任务结果编码破坏相关。成年期的丘脑抑制没有长期的后果。在成年期执行认知任务时兴奋丘脑可以挽救前额叶互相关性、任务结果编码和认知缺陷。这些数据表明青春期是丘脑皮质回路成熟的敏感窗口。此外，通过支持前额叶网络活动，增强丘脑活动为挽救神经发育障碍中的认知缺陷提供了潜在的治疗策略。