Sleep serves a number of functions, and many studies have suggested that sleep plays a role in memory storage and synaptic plasticity. The goal of our research is to define how sleep and sleep deprivation modulate the consolidation of long-term memory and how these processes are altered with age. Because aging is accompanied by alterations in both sleep and memory storage, definingthe role of sleep in memory storage may help us understand the behavioral, cellular and molecular changes that occur during aging and enable us to identify therapeutic approaches that might reverse these alterations. Although sleep and memory havebeen found to change with age in humans and rodents, it is not known howthe modulationof memory storage by sleep and sleep deprivation changes across the lifespan. Declarative memory,which is mediated by the hippocampal system, appears to be especially prone to age-related impairments. Sleep changes observed with aging include increased sleep fragmentation, decreased slow wave sleep, decreased delta power and decreased sleep homeostasis. What are the consequences of these changes in sleep? How do these changes affect the function of sleep? The experiments in this project focus on examining the effects of sleep deprivation on memory storage at various ages. Our work reveals that sleep deprivation during a specific time window after training selectively impairs memory for contextual fear conditioning in young adult mice, suggesting that sleep deprivation may selectively alter processes in the hippocampus necessary for memory consolidation. We are interested in bridging behavioral studies, which have shown that sleep is needed for the consolidation of memory, with current knowledge about the cellular and molecular mechanisms of memory storage to understand how sleep, sleep deprivation and memory interact across the lifespan. Our proposed research begins by defining the behavioral effects of sleep deprivation on memory storage in young adult, middle aged and old mice (SpecificAim i). We then examine how sleep is altered during the consolidation of contextual fear conditioning (Specific Aim 2).
In Specific Aim 3, we determine the cellular impact of sleep deprivation by studying the effects of sleep deprivation on hippocampal synaptic plasticity. Our gene expression experiments in Specific Aim 4 will provide a comprehensive survey of the molecular effects of sleep deprivation in the hippocampus and relate these alterations in gene expression to the changes in gene expression that occur following fear conditioning. Together, the proposed experiments will define how sleep deprivation and sleep modulate memory consolidation across the lifespan and will identify the molecular and cellular mechanisms by which sleep deprivation impairs memory storage.
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