Abstract
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-h 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.