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）的病因学假设机制。在感觉皮层中，丘脑在产后敏感期传递的活动对于皮层的正常成熟至关重要。丘脑活动是否也会影响前额皮质成熟尚不清楚。我们表明，在青春期抑制小鼠的背中和中线丘脑会导致丘脑 - 前额叶投射密度的长期下降和对前额叶神经元的兴奋性驱动减少。它还在成年期导致前额叶依赖性认知缺陷，与前额叶交叉相关和任务结果编码中断有关。成年期的丘脑抑制没有长期影响。在认知任务期间刺激成年期的丘脑挽救了前额交叉相关、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，通过支持前额网络活动，促进丘脑活动为挽救神经发育障碍的认知缺陷提供了一种潜在的治疗策略。