Effect of Acute Enriched Environment Exposure on Brain Oscillations and Activation of the Translation Initiation Factor 4E-BPs at Synapses across Wakefulness and Sleep in Rats.

Abstract

Brain plasticity is induced by learning during wakefulness and is consolidated during sleep. But the molecular mechanisms involved are poorly understood and their relation to experience-dependent changes in brain activity remains to be clarified. Localised mRNA translation is important for the structural changes at synapses supporting brain plasticity consolidation. The translation mTOR pathway, via phosphorylation of 4E-BPs, is known to be activate during sleep and contributes to brain plasticity, but whether this activation is specific to synapses is not known. We investigated this question using acute exposure of rats to an enriched environment (EE). We measured brain activity with EEGs and 4E-BP phosphorylation at cortical and cerebellar synapses with Western blot analyses. Sleep significantly increased the conversion of 4E-BPs to their hyperphosphorylated forms at synapses, especially after EE exposure. EE exposure increased oscillations in the alpha band during active exploration and in the theta-to-beta (4-30 Hz) range, as well as spindle density, during NREM sleep. Theta activity during exploration and NREM spindle frequency predicted changes in 4E-BP hyperphosphorylation at synapses. Hence, our results suggest a functional link between EEG and molecular markers of plasticity across wakefulness and sleep.