Sleep and Associative Memory Formation in Aplysia

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DESCRIPTION (provided by applicant): Memory formation represents a dynamic process modulated by multiple factors including the circadian clock and sleep. In the past few decades, sleep loss and sleep deprivation have developed into major societal problems with individuals working longer hours, fragmented sleep patterns due to shift work, technological interferences and social jet lag. Sleep loss and sleep deprivation exact a heavy toll on society and individuals through increased traffic accidents, increased industrial and occupational accidents, and decreased productivity and performance. Sleep deprivation causes significant decrements in short and long-term memory. In order to ameliorate the consequences of sleep deprivation, it is necessary to understand how systems level problems and changes in behavior affect molecular and cellular processes at the level of individual neuronal circuits and neuron groups. Defining the mechanisms through which sleep and sleep loss impact memory formation is crucial to identifying methods to optimize performance and health in modern society. Given the high molecular conservation underlying memory formation across species, the marine mollusk Aplysia californica with its simple neural circuitry provides an ideal model for detailing in vivo interactions between sleep, the circadian clock and memory. Previously, we described short, intermediate and long-term memory for an operant learning paradigm, learning that food is inedible (LFI). We have characterized sleep in Aplysia and found that Aplysia sleep patterns resemble human sleep patterns with sleep occurring only at night in long consolidated bouts. Our long-term objective is to define the mechanisms through which the sleep deprivation affects the formation of associative memories and identify mechanisms through which the circadian clock and sleep interact to regulate memory. The goal of this proposal is to identify cellular changes and changes in gene expression caused by sleep deprivation specifically in the neurons involved in feeding behaviors and LFI memory and to identify genes and pathways necessary for long-term memory formation that are inhibited by sleep deprivation. These studies will further our understanding of the functions of sleep and importantly, provide a research base for future therapeutic treatments to improve memory and performance.