title: Extracellular signal-regulated kinase (ERK) activity during sleep consolidates cortical plasticity in vivo.
abstract: Ocular dominance plasticity (ODP) in the cat primary visual cortex (V1) is induced during waking by monocular deprivation (MD) and consolidated during subsequent sleep. The mechanisms underlying this process are incompletely understood. Extracellular signal-regulated kinase (ERK) is activated in V1 during sleep after MD, but it is unknown whether ERK activation during sleep is necessary for ODP consolidation. We investigated the role of ERK in sleep-dependent ODP consolidation by inhibiting the ERK-activating enzyme MEK in V1 (via U0126) during post-MD sleep. ODP consolidation was then measured with extracellular microelectrode recordings. Western blot analysis was used to confirm the efficacy of U0126 and to examine proteins downstream of ERK. U0126 abolished ODP consolidation and reduced both phosphorylation of eukaryotic initiation factor 4E (eIF4E) and levels of the synaptic marker PSD-95. Furthermore, interfering with ERK-mediated translation by inhibiting MAP kinase-interacting kinase 1 (Mnk1) with CGP57380 mimicked the effects of U0126. These results demonstrate that ODP consolidation requires sleep-dependent activation of the ERK-Mnk1 pathway.
authors.affiliation: Department of Neuroscience, School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Dumoulin
authors.affiliation: Department of Neuroscience, School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Aton
authors.affiliation: Department of Neuroscience, School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Watson
authors.affiliation: Department of Neuroscience, School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Renouard
authors.affiliation: Department of Neuroscience, School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Tammi
authors.initials: T
authors.lastname: Coleman
authors.affiliation: Department of Neuroscience, School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Marcos G
authors.initials: MG
authors.lastname: Frank
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002415:Cats; D023882:Dominance, Ocular / Q000187:drug effects / Q000502:physiology*; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D012683:Sensory Deprivation / Q000502:physiology*; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D014793:Visual Cortex / Q000187:drug effects / Q000201:enzymology*
chemical_list: D000814:Aniline Compounds; D002070:Butadienes; C466997:CGP 57380; D039561:Eukaryotic Initiation Factor-4E; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011687:Purines; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases
keywords: MAP kinase-interacting kinase; consolidation; monocular deprivation; ocular dominance; protein synthesis
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