Abstract
Arguably, humans spend, on average, a third of their lives sleeping. However, the real
function of sleep remains a matter of intense debate. One of the proposed functions for sleep is
that it is necessary for the consolidation of changes in synaptic communication (i.e. synaptic
plasticity) in response to experience during wakefulness. In this study, the influence of sleep
on brain plasticity was assessed with a particular emphasis on the effect it exerts on protein
translation in the cortex and cerebellum. Using rat model manipulations, the molecular
mechanisms of translation underlying synaptic plasticity influenced by sleep and experience
were investigated. The rats were exposed to different sleep/wake regimes, including extended
wake and enriched environment followed by sleep, then total brain lysate and synaptic-enriched
brain fractions from rats were used to assess how sleep after exposure to a novel environment
affects local translation at synapses. Analysis of the phosphorylation state of the translation
initiation activation marker 4EBP1 showed that it is hyperphosphorylated upon sleep compared
to those that were sleep deprived. Global phosphoprotemoic analysis showed increased
phosphorylation of synaptic proteins such as PSD-95, ARC and glutamate receptors. Moreover,
Polysome profiling followed by global analysis of translation rate of mRNA using RNA-seq
revealed increased mRNA levels on heavy polysomal fractions from animals that were
subjected to sleep and enriched environment compared to those that were sleep deprived.
Together, the results of this study show that sleep is key regulator of synaptic plasticity via
modulation of protein translation and phosphorylation.