Protein Synthesis during Sleep Consolidates Cortical Plasticity In Vivo

SummarySleep consolidates experience-dependent brain plasticity, but the precise cellular mechanisms mediating this process are unknown [1]. De novo cortical protein synthesis is one possible mechanism. In support of this hypothesis, sleep is associated with increased brain protein synthesis [2 and 3] and transcription of messenger RNAs (mRNAs) involved in protein synthesis regulation [4 and 5]. Protein synthesis in turn is critical for memory consolidation and persistent forms of plasticity in vitro and in vivo [6 and 7]. However, it is unknown whether cortical protein synthesis in sleep serves similar functions. We investigated the role of protein synthesis in the sleep-dependent consolidation of a classic form of cortical plasticity in vivo (ocular dominance plasticity, ODP; [8 and 9]) in the cat visual cortex. We show that intracortical inhibition of mammalian target of rapamycin (mTOR)-dependent protein synthesis during sleep abolishes consolidation but has no effect on plasticity induced during wakefulness. Sleep also promotes phosphorylation of protein synthesis regulators (i.e., 4E-BP1 and eEF2) and the translation (but not transcription) of key plasticity related mRNAs (ARC and BDNF). These findings show that sleep promotes cortical mRNA translation. Interruption of this process has functional consequences, because it abolishes the consolidation of experience in the cortex.

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► mTORC1 inhibition selectively impairs sleep-dependent cortical plasticity
► Sleep promotes translation factor regulation
► ARC and BDNF transcription and translation are divided across wake and sleep
► Transcription occurs in response to waking experience, but translation requires sleep