A. Five hours of total sleep deprivation reduces total protein levels of mTOR and mTOR phosphorylation in the hippocampus (n = 9 per group, **P < 0.005, *P < 0.01). All error bars denote s.e.m. Adapted from Vecsey, et al., 2012. [7] B. pCREB immunoreactivity in area CA1 of the hippocampus is elevated during NREM sleep (n = 5-8 per group, P< 0.05).Adapted from Luo, et al., 2013. [16] C. Representative images of pCREB immunoreactivity in area CA1 of the hippocampus is reduced after 5 hours of sleep deprivation. D. PDE4 activity was significantly upregulated in hippocampi from mice deprived of sleep for 5 hours (P = 0.039). E. The PDE4 isoform PDE4A5 was significantly upregulated by sleep deprivation in the hippocampus (P = 0.033). C-D Adapted from Vecsey, et al., 2009. [17] F. Effect of previous novelty experience on zif-268 brain expression during waking and sleep states. Shown are autoradiograms of brain sections whose gene expression levels best represent the means for each group studied. In controls, zif-268 expression decreased from WK (F1) to SW (F1′) and REM (F1″). In enriched environment animals, zif-268 levels decreased from WK (F2) to SW (F2′), but increased from the latter to REM (F2″). This effect was particularly noticeable in the cerebral cortex and the hippocampus. Adapted from Riberio, et al., 1999. [146] G. A schematic overview of hippocampal signaling pathways whose modulation by sleep deprivation may contribute to the effects of sleep deprivation on memory encoding and consolidation. Left Panel, signaling pathways under conditions of sleep. Right Panel, sleep deprivation has been reported to reduce glutamatergic signaling and attenuates cAMP signaling and CREB-mediated gene transcription. All of these molecular events are shown in a single connected pathway in order to demonstrate how the effects of sleep deprivation could potentially interact to impact learning and memory. Dashed black lines and blue arrows pointing down indicate attenuation of the signaling pathway. Red labels and lines indicate an increase of the signaling pathway.