Sleep loss or insomnia is among the contributing factors of cognitive deficit, the underlying mechanisms of which remain largely elusive. The endocannabinoid (eCB) system plays a role in sleep, while it is unknown if it is involved in the regulation of memory retrieval by sleep deprivation. In addition, it still controversial how rapid-eye-movement sleep deprivation (REMSD) affects the spatial memory of adolescent mice. Here, we found that 24-hour REMSD impairs spatial memory retrieval of adolescent mice in an object-place recognition task, which was rescued by NESS0327, a neutral cannabinoid receptor 1 (CB1R) antagonist. Mechanistically, REMSD induced eCB-mediated short-term and long-term synaptic plasticity changing including depolarization-induced suppression of inhibition (DSI) in the pyramidal neurons of the hippocampus, in which long-term synaptic plasticity changing was rescued by NESS0327. REMSD downregulated monoacylglycerol lipase, a hydrolase for the endocannabinoid 2-arachidonoylglycerol (2-AG), suggesting the involvement of eCB accumulation and the consequent synaptic plasticity in REMSD-elicited memory impairment in adolescent mice. These findings shed light on the role of sleep disorders in learning and memory deficit of adolescents.

睡眠不足或失眠是认知障碍的诱因之一，其潜在机制仍难以捉摸。内源性大麻素（eCB）系统在睡眠中发挥作用，但尚不清楚它是否参与睡眠剥夺对记忆恢复的调节。此外，仍然存在争议的是快速眼动睡眠剥夺（REMSD）如何影响青春期小鼠的空间记忆。在这里，我们发现24小时REMSD会损害中性大麻素受体1（CB1R）拮抗剂NESS0327拯救的对象位置识别任务中的青春期小鼠的空间记忆检索能力。从机理上讲，REMSD诱导eCB介导的短期和长期突触可塑性改变，包括去极化诱导的海马锥体神经元抑制（DSI）抑制，NESS0327挽救了长期突触可塑性的改变。REMSD下调了单酰基甘油脂肪酶，这是一种内源性大麻素2-花生四烯酸甘油酯（2-AG）的水解酶，表明eCB的积累和突触可塑性参与了REMSD引起的青春期小鼠的记忆障碍。这些发现揭示了睡眠障碍在青少年学习和记忆不足中的作用。