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.

Hippocampal Network Oscillations Rescue Memory Consolidation Deficits Caused by Sleep Loss

“…( Vecsey et al 2009 ; Aton et al 2009a ; Seibt et al 2012 ; Dumoulin et al 2015 ; Havekes et al 2016 ; Tudor et al 2016 )Recent findings have shown that coherent rhythms of activity between brain areas (e.g., between hippocampus and cortex) are associated with memory storage across a period of sleep ( Rothschild et al 2017 ; Totty et al 2017 ; Xia et al 2017 ). An unanswered question is how these oscillations are coordinated between thalamocortical circuits and the hippocampus.…”

Two-Stage Translational Control of Dentate Gyrus LTP Consolidation Is Mediated by Sustained BDNF-TrkB Signaling to MNK

“…(Dumoulin et al, 2013;Panja et al, 2009;Figures S6A and S6B). However, in vitro kinase assays show that CGP57380 inhibits other kinases (MKK1, CK1, BRSK2) in addition to MNK1 and MNK2 (Bain et al, 2007).…”

Sleep, synaptic homeostasis and neuronal firing rates

“…Two underlying mechanisms have been proposed. One involves the activation of the ERK-MEK pathway during early sleep (but not wake) immediately after MD [39], and the other involves a rapid switch in the excitation/inhibition balance [40]. Indeed, likely because of its short duration, MD in cats does not decrease the firing of pyramidal neurons responding to the deprived eye, but reduces those of fast spiking interneurons, prompting the authors to propose that reduced inhibition may account for the later increased firing during sleep of the pyramidal cells responding to the open eye [40].…”