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Title: Is expression of synaptic plasticity-related genes modulated by exposure to novelty during subsequent sleep?
Authors: Calais, Julien Brag
Ojopi, Elida Benquique
Ribeiro, Sidarta Tollendal Gomes
Morya, Edgard
Nicolelis, Miguel Angelo Laporta
Sameshima, Koichi
Keywords: Sleep;Memory;Synaptic Plasticity;Immediate Early Genes;Protein Phosphatase 2A
Issue Date: Sep-2010
Portuguese Abstract: Independent lines of evidence support the role of sleep in memory consolidation. However, some contradictory findings have been observed regarding how synaptic plasticity is modulated during sleep. Sleep deprivation studies have shown that the expression of genes related to long-term depression (LTD) is increased during sleep, while the expression of genes related to long-term potentiation (LTP) is increased during waking. However, experiments involving exposure to novelty and/or training in behavioral tasks prior to sleep have shown that immediate early genes (IEG) related to LTP maintenance, such Arc and Egr1, are reinduced during REM sleep. To further explore this question, we examined whether exposure to novelty influences the expression of genes related to LTP (Arc, Bdnf, Creb1, Egr1, Egr2, Fos, Nr4a1) or LTD (Camk4, Ppp2ca, Ppp2r2d). Behaviors and local field potentials (LFPs) were recorded from the hippocampus and primary somatosensory cortex of 30 adult male rats. Recordings were performed before, during and after 20 min of exposure to four novel objects. Animals were prevented from sleeping for 60 minutes after exposure, and were then allowed to sleep freely. Unexposed animals served as negative controls. Immediately after sleep deprivation (waking groups) or thirty minutes after entering sleep (slow wave sleep and REM sleep groups), animals were euthanized, and their brains were dissected into frozen samples of somatosensory cortex and hippocampus. Finally, plasticity-related genes had their expression levels analyzed by real time PCR. A bootstrap non-parametric two-way ANOVA (NANOVA) was performed on the data, followed when appropriate by the Tukey HSD test corrected for the number of comparisons (.α = 0.05). We observed an increase in gene expression in hippocampus of animals that were exposed to novel spatio-sensory stimuli in comparison to control animals after waking (Arc - p=0.001; Egr1 - p=0.005; Fos - p<0.001; Nr4a1 - p=0.006; Ppp2ca - p=0.018) and REM sleep (Arc - p=0.030; Egr1 - p=0.001; Fos - p<0.001; Ppp2ca - p=0.037; Ppp2r2d - p=0.010), but not after slow wave sleep. These findings corroborate the important role of REM sleep for memory consolidation. Most importantly, our results provide pioneering experimental evidence that synaptic potentiation and depression occur concomitantly during REM sleep.
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