Although the underlying mechanism is not elucidated, it has been postulated repeatedly that deprivation of sleep, particularly rapid eye movement (REM) sleep, affects learning. Here we report that memory for newly acquired information is impaired after a specific period of REM sleep deprivation (REMD). Memory retrieval-induced phosphorylation of protein kinases in the rat amygdala is abrogated by REMD that is associated with an increase in the expression of a dual protein/lipid phosphatase PTEN. REMD given before training is without effect, suggesting the lack of effect on the acquisition of memory. Intra-amygdala administration of antisense but not sense or scrambled oligonucleotides for PTEN prevents REMD-induced decrease in protein phosphorylation and impairment of fear memory. Thus, REMD interferes with the process of memory retention via the activation of PTEN.
