Schizophrenia is associated with alterations of sensory integration, cognitive processing and both sleep architecture and sleep oscillations in mouse models and human subjects, possibly through changes in thalamocortical dynamics. Oxidative stress (OxS) damage, including inflammation and the impairment of fast-spiking gamma-aminobutyric acid neurons have been hypothesized as a potential mechanism responsible for the onset and development of schizophrenia. Yet, the link between OxS and perturbation of thalamocortical dynamics and sleep remains unclear. Here, we sought to investigate the effects of OxS on sleep regulation by characterizing the dynamics of thalamocortical networks across sleep-wake states in a mouse model with a genetic deletion of the modifier subunit of glutamate-cysteine ligase (Gclm knockout, KO) using high-density electrophysiology in freely-moving mice. We found that Gcml KO mice exhibited a fragmented sleep architecture and impaired sleep homeostasis responses as revealed by the increased NREM sleep latencies, decreased slow-wave activities and spindle rate after sleep deprivation. These changes were associated with altered bursting activity and firing dynamics of neurons from the thalamic reticularis nucleus, anterior cingulate and anterodorsal thalamus. Administration of N-acetylcysteine (NAC), a clinically relevant antioxidant, rescued the sleep fragmentation and spindle rate through a renormalization of local neuronal dynamics in Gclm KO mice. Collectively, these findings provide novel evidence for a link between OxS and the deficits of frontal TC network dynamics as a possible mechanism underlying sleep abnormalities and impaired homeostatic responses observed in schizophrenia.

精神分裂症与小鼠模型和人类受试者的感觉统合、认知处理以及睡眠结构和睡眠振荡的改变有关，可能是通过丘脑皮质动力学的变化。氧化应激 (OxS) 损伤，包括炎症和快速刺激的 γ-氨基丁酸神经元损伤，已被假设为导致精神分裂症发病和发展的潜在机制。然而，OxS 与丘脑皮质动力学和睡眠扰动之间的联系仍不清楚。在这里，我们试图通过表征小鼠模型中睡眠-觉醒状态下丘脑皮质网络的动态来研究 OxS 对睡眠调节的影响，该模型具有谷氨酸-半胱氨酸连接酶修饰亚基的遗传缺失（Gclm 敲除）, KO) 在自由移动的小鼠中使用高密度电生理学。我们发现Gcml KO 小鼠表现出碎片化的睡眠结构和受损的睡眠稳态反应，如 NREM 睡眠潜伏期增加、睡眠剥夺后慢波活动和纺锤波率降低所揭示的那样。这些变化与来自丘脑网状核、前扣带回和前背丘脑的神经元的爆发活动和放电动力学改变有关。N-乙酰半胱氨酸 (NAC) 是一种临床相关的抗氧化剂，通过Gclm中局部神经元动力学的重新正常化，挽救了睡眠片段化和纺锤波率敲老鼠。总的来说，这些发现为 OxS 与额叶 TC 网络动力学缺陷之间的联系提供了新的证据，作为在精神分裂症中观察到的睡眠异常和受损的稳态反应的潜在机制。