Date of Award

2013

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Neuroscience

First Advisor

Marcos G. Frank

Abstract

Despite decades of research, the function of sleep remains controversial. One theory is that sleep plays a role in consolidating plasticity induced during prior waking. Ocular dominance plasticity (ODP) in the cat visual cortex is induced during waking monocular deprivation (MD) and consolidated during subsequent sleep. Extracellular signal-regulated kinase (ERK) signaling is required for ODP and is elevated during post-MD sleep, but its requirement during sleep is unknown. In Chapter 2, we investigated whether ERK activity is required during sleep for ODP consolidation by inhibiting the upstream activator of ERK (MEK) with intracortical infusions of U0126 into V1 during post-MD sleep. ERK inhibition abolished ODP consolidation, as measured by extracellular single unit recording. Furthermore, ERK inhibition reduced phosphorylation of eukaryotic initiation factor 4E (eIF4E) and post-synaptic density protein 95 (PSD-95) levels. MAP kinase-interacting kinase 1 (Mnk1) is activated by ERK and directly phosphorylates eIF4E; inhibition of Mnk1 mimicked the effects of ERK inhibition. These results show that activation of the ERK-Mnk1 pathway during post-MD sleep is required for ODP consolidation, and that this pathway promotes the synthesis of plasticity-related proteins such as PSD-95. However, sleep can be broadly subdivided into rapid eye movement (REM) and non-REM (NREM) sleep, but the relative contributions of these states to ODP and the ERK pathway are unknown. In Chapter 3, we examined whether REM sleep is required for ODP consolidation and ERK activation by depriving animals of REM sleep following six hours of waking MD. REM sleep deprivation (RSD) abolished ODP consolidation, as measured by optical imaging of intrinsic cortical signals, and reduced ERK phosphorylation in V1. These effects were not seen in a group that received NREM-fragmented sleep (as a control for the nonspecific effects of RSD). Furthermore, ODP and ERK phosphorylation correlated with the degree of beta-gamma activity in V1 during REM sleep, suggesting that neuronal activity patterns during REM promote ERK activation and ODP consolidation. Together, the findings in the following chapters suggest that, following the induction of cortical plasticity during waking, the ERK-Mnk1 pathway is activated during REM sleep, promoting the synthesis of plasticity-related proteins to consolidate cortical plasticity.

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