title: Protein synthesis during sleep consolidates cortical plasticity in vivo.
abstract: Sleep 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, 3] and transcription of messenger RNAs (mRNAs) involved in protein synthesis regulation [4, 5]. Protein synthesis in turn is critical for memory consolidation and persistent forms of plasticity in vitro and in vivo [6, 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, 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.
authors.affiliation: Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6074, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Seibt
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Dumoulin
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Aton
authors.forename: Tammi
authors.initials: T
authors.lastname: Coleman
authors.forename: Adam
authors.initials: A
authors.lastname: Watson
authors.forename: Nirinjini
authors.initials: N
authors.lastname: Naidoo
authors.forename: Marcos G
authors.initials: MG
authors.lastname: Frank
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D002415:Cats; D023882:Dominance, Ocular; D056892:Mediator Complex / Q000235:genetics; D009473:Neuronal Plasticity / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis / Q000502:physiology*; D012890:Sleep / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014158:Transcription, Genetic; D014851:Wakefulness / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C113182:DRIP, VDR interacting protein complex; D056892:Mediator Complex; D010750:Phosphoproteins; D058570:TOR Serine-Threonine Kinases